Sample records for bile ducts

... of bileduct cancer. The rest of this document refers only to cholangiocarcinomas. Benign bileduct tumors ... tumors, which aren’t discussed further in this document. Other cancers in the liver The most common ...

Common bileduct stones (CBDSs) are solid deposits that can either form within the gallbladder or migrate to the common bileduct (CBD), or form de novo in the biliary tree. In the USA around 15% of the population have gallstones and of these, 3% present with symptoms annually. Because of this, there have been major advancements in the management of gallstones and related conditions. Management is based on the patient's risk profile; young and healthy patients are likely to be recommended for surgery and elderly patients with comorbidities are usually recommended for endoscopic procedures. Imaging of gallstones has advanced in the last 30 years with endoscopic retrograde cholangiopancreatography evolving from a diagnostic to a therapeutic procedure in removing CBDSs. We present a complicated case of a patient with a CBDS and periampullary diverticulum and discuss the techniques used to diagnose and remove the stone from the biliary system. PMID:23946532

Common bileduct stones (CBDSs) are solid deposits that can either form within the gallbladder or migrate to the common bileduct (CBD), or form de novo in the biliary tree. In the USA around 15% of the population have gallstones and of these, 3% present with symptoms annually. Because of this, there have been major advancements in the management of gallstones and related conditions. Management is based on the patient's risk profile; young and healthy patients are likely to be recommended for surgery and elderly patients with comorbidities are usually recommended for endoscopic procedures. Imaging of gallstones has advanced in the last 30 years with endoscopic retrograde cholangiopancreatography evolving from a diagnostic to a therapeutic procedure in removing CBDSs. We present a complicated case of a patient with a CBDS and periampullary diverticulum and discuss the techniques used to diagnose and remove the stone from the biliary system. PMID:23946532

Bileduct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bileduct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bileduct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity

Objective. To describe the intrahepatic bileduct transposition (anatomical variation occurring in intrahepatic ducts) and to determine the frequency of this variation. Material and Methods. The researches were performed randomly on 100 livers of adults, both sexes. Main research methods were anatomical macrodissection. As a criterion for determination of variations in some parts of bile tree, we used the classification of Segmentatio hepatis according to Couinaud (1957) according to Terminologia Anatomica, Thieme Stuugart: Federative Committee on Anatomical Terminology, 1988. Results. Intrahepatic transposition of bileducts was found in two cases (2%), out of total examined cases (100): right-left transposition (right segmental bileduct, originating from the segment VIII, joins the left liver duct-ductus hepaticus sinister) and left-right intrahepatic transposition (left segmental bileduct originating from the segment IV ends in right liver duct-ductus hepaticus dexter). Conclusion. Safety and success in liver transplantation to great extent depends on knowledge of anatomy and some common embryological anomalies in bile tree. Variations in bile tree were found in 24–43% of cases, out of which 1–22% are the variations of intrahepatic bileducts. Therefore, good knowledge on ductal anatomy enables good planning, safe performance of therapeutic and operative procedures, and decreases the risk of intraoperative and postoperative complications. PMID:22550601

... the liver. It contains cholesterol, bile salts, and waste products such as bilirubin . Bile salts help your ... can lead to life-threatening infection and a dangerous buildup of bilirubin. If the blockage lasts a ...

In recent years, laparoscopic common bileduct exploration has become the procedure of choice in the management of choledocholithiasis in several laparoscopic centers. The increasing interest for this laparoscopic approach is due to the development of instrumentation and technique, allowing the procedure to be performed safely, and it is also the result of the revised role of endoscopic retrograde cholangiopancreatography, which has been questioned because of its cost, risk of complications and effectiveness. Many surgeons, however, are still not familiar with this technique. In this article we discuss the technique and results of laparoscopic common bileduct exploration. Both the laparoscopic transcystic approach and choledochotomy are discussed, together with the results given in the literature. When one considers the costs, morbidity, mortality and the time required before the patient can return to work, it would appear that laparoscopic cholecystectomy with common bileduct exploration is more favorable than open surgery or laparoscopic cholecystectomy with preoperative or postoperative endoscopic sphincterotomy. However, the technique requires advanced laparoscopic skills, including suturing, knot tying, the use of a choledochoscope, guidewire, dilators and balloon stone extractor. Although laparoscopic common bileduct exploration appears to be the most cost-effective method to treat common bileduct stones, it should be emphasized that this procedure is very challenging, and it should be performed by well-trained laparoscopic surgeons with experience in biliary surgery. PMID:11981684

... for bileduct cancer? What are the key statistics about bileduct cancer? Bileduct cancer is ... it is when it is found. For survival statistics, see the section “ Survival statistics for bileduct ...

... bile builds up in the liver, and jaundice (yellow color of the skin) develops due to the increasing ... upper right side Dark urine Fever Itching Jaundice (yellow skin color) Nausea and vomiting Pale-colored stools

... line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline ... common bileduct. A small amount of contrast dye is injected through the tube to help outline ...

... form of radiation for bileduct cancer. External beam radiation therapy (EBRT) This type of radiation therapy ... determine the correct angles for aiming the radiation beams and the proper dose of radiation. The treatment ...

We are not in agreement with the opinion that the credit for excellent results after laparoscopic cholecystectomy is to be attributed to the routine performing of intraoperative cholangiography. We performed 2538 laparoscopic cholecystectomies without routine intraoperative cholangiography and we obtained very low rate and severity of common bileduct injuries: there was a total of four common bileduct injuries (0.16%), in no case was the injury a major transaction, and injuries were detected intraoperatively and easily repaired with a T-tube. Cholangiography could prevent bileduct transaction, but that it is not necessary for intraoperative cholangiography to be routinely performed for this purpose. It is sufficient for intraoperative cholangiography to be performed whenever the surgeon is in doubt as to the biliary anatomy or common bileduct clearance, and that when dissection of the cholecystic peduncle proves difficult he does not hesitate to convert to open access. PMID:16333543

... duct cancer be prevented? Do we know what causes bileduct cancer? We don’t know the exact cause of ... to top » Guide Topics What Is BileDuct Cancer? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and ...

The neurogenic tumors in the biliary tract are rare and usually are amputation neuroma that occur after cholecystectomy. We describe a case of isolated neurofibroma of the common bileduct in a young man not cholecystectomized. The patient suffered recurrent episodes of abdominal pain, vomiting and weight loss without clinical signs of Von Recklinghausen's disease or jaundice. The hepatogram was normal. The echography indicated a solid formation with obstruction of the proximal common bileduct. In the ERCP the stenosis was found. Surgical excision of the tumor and anastomosis of bilateral hepatic ducts and jejunum were carried out. At microscopic examination intraparietal neurofibroma of the common bileduct was found. As isolated entity, we know of only one reported case. PMID:8731581

It is imperative for gastroenterologists to understand the different formations of bileduct stones and the various medical treatments available. To minimize the complications of endoscopic retrograde cholangiopancreatography (ERCP), it is critical to appropriately assess the risk of bileduct stones before intervention. Biliary endoscopists should be comfortable with the basic techniques of stone removal, including sphincterotomy, mechanical lithotripsy, and stent placement. It is important to be aware of advanced options, including laser and electrohydraulic stone fragmentation, and papillary dilatation for problematic cases. The timing and need for ERCP in those who require a cholecystectomy is also a consideration. PMID:23540960

A fundamental guideline for the use of test results concerning liver, bileduct and pancreatic diseases was proposed in 1991 from the Japan Society of Clinical Pathology (JSCP). This guideline was principally based on the document of 1988 from the Committee on liver function tests of the Japanese Society of Gastroenterology (JSG). The document from the JSG was revised in May, 1994. Also a guideline for selection of markers of hepatitis virus in hepatic disorders, was proposed in January, 1994 from the same Committee of JSG. Here, we reevaluated and discussed the JSCP guideline as taking into consideration the two 1994 JSG documents. PMID:7602802

The poor prognosis of extrahepatic bileduct carcinoma makes early detection and diagnosis essential for positive patient outcomes. We describe 2 cases of jaundice-free early extrahepatic bileduct carcinoma detected by magnetic resonance cholangiopancreatography. Extrahepatic bileduct carcinoma was discovered incidentally in patient 1 by magnetic resonance cholangiopancreatography during evaluation of a gallbladder stone. In patient 2, extrahepatic bileduct carcinoma was found during a routine health maintenance exam. Both patients underwent radical surgical intervention. Both patient 1 and 2 have remained in good health for over one year, 3.5 and one year, respectively, and have not exhibited any signs or symptoms of relapse or cancer recurrence. Based on these cases, it appears that magnetic resonance cholangiopancreatography can play a significant role in the early detection of extrahepatic bileduct carcinoma and improve disease prognosis. PMID:15816438

It is known that the fluids bathing tumors might contain a higher level of the carcinoembryonic antigen (CEA) than those found in the blood. Therefore, we evaluated the role of bile CEA in diagnosing bileduct cancer. One hundred and thirty two patients were prospectively studied. The patients were divided into 3 groups: the bileduct cancer (n=32), pancreatic cancer (n=16), and benign biliary diseases (n=84) groups. Bile samples were obtained on the next day of the biliary drainage procedures. The mean bile CEA level in those with bileduct cancer (120.6 +/- 156.9 ng/mL) was significantly higher than those with pancreatic cancer and benign biliary diseases (32.0 +/- 28.5 ng/mL, 29.3 +/- 56.3 ng/mL). Using the level of 20 ng/mL, the sensitivity and specificity of bile CEA in the diagnosis of bileduct cancer from benign biliary diseases were 65.6% and 66.7%, respectively. Both the bile CEA and total bilirubin level were found to be an independent factor linked to bileduct cancer. This study result suggests that bile CEA level is a useful supplementary test for diagnosing bileduct cancer. PMID:14676443

Background: Postoperative bile leak secondary to a fistula is a known complication of hepatic surgery. Four different biliary fistula sub-types have been described: type A refers to minor leakage from the bileduct stump; type B to major leakage caused by insufficient closure of the bileduct stump; type C to major leakage caused by injury to the bileduct, and type D (the rarest) to the division and exclusion of a bileduct. This complication results from functional liver parenchyma in which bile drainage is excluded from the main duct. Methods: A retrospective review of the database for 163 patients diagnosed with post-hepatic surgery bile leak from April 1992 to June 2007 was performed. Results: Three patients were found to have type D biliary fistula, with durations of 3–21 months. The bile leak developed after a right hepatectomy in two patients and a right hepatectomy extending to segment IV in one patient. All three patients were rescheduled for surgical exploration, following failure of medical treatment. The procedure consisted of repeat resection of the independent liver parenchyma containing the fistula. One patient developed a postoperative leak from a hepaticojejunal anastomosis (treated conservatively) and the other two patients had an uneventful recovery. No recurrence of bile leak was encountered during their follow-up. Conclusions: Our experience indicates that conservative treatment is deceptive and not efficacious. For this condition, surgical intervention is the treatment of choice because it is very effective and is associated with a low morbidity. PMID:19718366

Though variations of intrahepatic biliary anatomy are quite common, duplication of the extrahepatic biliary system is extremely rare and reported infrequently in the literature. Laparoscopic cholecystectomy is one of the most common general surgery procedures performed. Unfortunately, iatrogenic bileduct injuries can contribute to significant morbidity including hospital readmissions, infectious complications and death. Anomalous extrahepatic biliary anatomy may be one of the factors, which increases the likelihood of bileduct injury during laparoscopic cholecystectomy. We present a case of an iatrogenic bileduct injury that occurred during a laparoscopic cholecystectomy, in which a duplicated extrahepatic biliary system was identified intraoperatively during the definitive operative repair. PMID:27141049

... the large intestine called ulcerative colitis. Bileduct stones , which are similar to, but much smaller than ... between ulcerative colitis and primary sclerosing cholangitis. Older age Older people are more likely than younger people ...

In this report, an adult patient with tubulopapillary adenoma of the common bileduct that manifested with jaundice is presented. Diagnostic challenges were analyzed. Although adenomas of the common bileduct are rare, they should be kept in mind in the differentiation of lesions of this region. It should be remembered that these lesions radiologically could mimic carcinoma and choledocholithiasis. Endoscopic resection should be considered as the primary method for treatment. Histopathology is the gold standard in diagnosis. PMID:27528819

Intrahepatic cholangiocarcinomas were found at necropsy in two previously reported cases of congenital dilatation of the intrahepatic bileducts. The nature of the developmental abnormality is discussed and compared with other forms of biliary dilatation. Slow-flowing bile for many years probably leads to cholangiocarcinoma. Images PMID:4343747

The incidence of common bileduct (CBD) pathology in a group of patients with benign biliary disease (n = 505) was found to be 23.2 per cent. The spectrum included 111 patients (90.2 per cent) with CBD stones, 37 of whom (33.3 per cent) had no symptoms or findings pre-operatively indicating CBD involvement. Five patients had papillary stenosis, three had postoperative CBD strictures, one had a choledochal cyst and one had an external biliary fistula. Of the 100 CBDs measuring more than 10 mm in diameter, 90 harboured calculi. In the remaining 23 CBDs measuring less than 10 mm, calculi were present in 21. The presence of CBD calculi was demonstrated by intra-operative cholangiography in 49 patients. In the remaining patients (n = 74), the diagnosis of CBD pathology was made either by percutaneous transhepatic cholangiography, endoscopic retrograde cholangio-pancreatography, T-tube cholangiography or peroperative palpation. The surgical procedures performed included choledochotomy and T-tube drainage (n = 74), transduodenal sphincteroplasty (n = 27) and choledochoduodenostomy (n = 18). The overall mortality and morbidity of CBD exploration was 3.3 per cent and 24.4 per cent respectively, which was significantly greater than that for cholecystectomy alone (0.3 per cent and 8.6 per cent respectively). Transduodenal sphincteroplasty carried a much higher mortality (11 per cent) and morbidity (52 per cent) when compared with other procedures. PMID:3167536

In sarcoidosis, granulomas are frequently present in multiple organs, including the liver. Typically, epithelioid granulomas (noncaseating) are scattered throughout the liver, but confluent granulomas can be present in cases with severe hepatic involvement. The characteristic inclusions in giant cells (for example, Schaumann bodies and asteroid bodies) are not seen in all cases and are not pathognomonic. The granulomas of sarcoidosis may heal without a trace, but confluent granulomas can result in extensive, irregular scarring. Occlusion of intrahepatic portal vein branches by the granulomatous inflammation probably accounts for the development of portal hypertension in some cases. A granulomatous cholangitis leading to ductopenia seems to be the underlying pathogenetic mechanism of the chronic cholestatic syndrome of sarcoidosis. Recognition of this syndrome is important in the differential diagnosis of other chronic cholestatic diseases, such as primary biliary cirrhosis or primary sclerosing cholangitis. Other rare complications of sarcoidosis are the Budd-Chiari syndrome and obstructive jaundice attributable to hepatic hilar lymphadenopathy or strictures of the bileducts. PMID:9581591

Background and Aim The function of the common bileduct is to transport bile from the liver and the gall bladder to the duodenum. Since the bileduct is a distensible tube consisting mainly of connective tissue, it is important to obtain data on the passive mechanical wall properties. The aims of this study were to study morphometric and biomechanical wall properties during distension of the bileduct. Methods Ten normal porcine common bileducts were examined in vitro. A computer-controlled volume ramp infusion system with concomitant pressure recordings was constructed. A video camera provided simultaneous measurement of outer dimensions of the common bileduct. Wall stresses and strains were computed. Results The common bileduct length increased by 25% from 24.4 ± 1.8 mm at zero pressure to 30.5 ± 2.0 mm at 5 kPa (p < 0.01). The diameter increased less than 10% in the same pressure range from 8.6 ± 0.4 mm to 9.3 ± 0.4 mm (p < 0.01). The stress-strain relations showed an exponential behavior with a good fit to the equation: σ = α . (exp(βε) - 1). The circumferential stress-strain curve was shifted to the left when compared to the longitudinal stress-strain curve, i.e. the linear constants (α values) were different (p < 0.01) whereas the exponential constants (β values) did not differ (p > 0.5). Conclusion The porcine bileduct exhibited nonlinear anisotropic mechanical properties. PMID:15260881

A 74-year-old man presented to a physician with a chief complaint of jaundice. He was diagnosed with bileduct carcinoma and admitted to our hospital. Laboratory data revealed abnormally elevated levels of total bilirubin, serum hepatic transaminase, and CA19-9. Endoscopic retrograde cholangiopancreatography revealed neoplastic stenosis from the hilus hepatis to the common bileduct. Abdominal computed tomography (CT) revealed an enhancing tumor in the hilus hepatis bileduct, and positron emission tomography-CT (PET-CT) revealed abnormal fluorodeoxyglucose accumulation in the tumor. Under a diagnosis of hilar cholangiocarcinoma, the patient underwent an extended right hepatectomy and left hepatico -jejunostomy. Immunohistochemically, the tumor cells were positive for neuroendocrine markers such as chromogranin A, synaptophysin, and CD56. The tumor was diagnosed as primary neuroendocrine carcinoma of the bileduct. The patient exhibited multiple liver metastasis 6 months after the operation. Transcatheter arterial chemoembolization (TACE) was performed for the liver metastasis. Although TACE exerted a cytoreductive effect temporarily, multiple liver abscesses developed. The patient died of liver failure 16 months after the operation. We report this rare case of primary neuroendocrine carcinoma of the bileduct. PMID:23267998

Bileduct stenosis, in most cases, appears to be the consequence of pancreatic head, ampulla of Vater and bileduct tumours, cholangitis sclerosans, as well as iatrogenic damages, which may all be diagnosed during endoscopic retrograde cholangiopancreatography (ERCP). In very rare cases the restriction may result from an atypically shaped wedged stone. This situation creates many diagnostic problems, which in the majority of cases can be solved using imaging studies. However, in some patients even a significant extension of diagnostic procedures may not lead to a correct diagnosis. We present a diagnostically difficult case of a deposit imitating restriction. We present a 70-year-old woman with common bileduct restriction undiagnosed despite several ultrasound examinations (USG), computed tomography (CT), double magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). Only after the third ERCP examination a fragmented, by formerly introduced prosthesis, deposit, imitating narrowing, was revealed. Identification of bileduct deposits depends on their composition, localisation and the imaging techniques used. Pigment calculi with atypical shape, bile density, air density or surrounding tissue density are very difficult to diagnose. Thus, the sensitivity of common bileduct stone detection in USG, CT, MRCP and endoscopic ultrasound (EUS) is 5–88%; 6–88%; 73–97%; and 84–98%, respectively. Moreover, ERCP may not diagnose the character of the restriction even in 5.2% up to 30% of the patients. Consequently, assessment of diagnosis in a number of patients is difficult. A deposit imitating common bileduct (CBD) restriction is a rare, difficult to diagnose phenomenon, which should be taken into account during differential diagnosis of CBD restrictions. PMID:25061493

Endoscopy is widely accepted as the first treatment option in the management of bileduct stones. In this review we focus on the alternative endoscopic modalities for the management of difficult common bileduct stones. Most biliary stones can be removed with an extraction balloon, extraction basket or mechanical lithotripsy after endoscopic sphincterotomy. Endoscopic papillary balloon dilation with or without endoscopic sphincterotomy or mechanical lithotripsy has been shown to be effective for management of difficult to remove bileduct stones in selected patients. Ductal clearance can be safely achieved with peroral cholangioscopy guided laser or electrohydraulic lithotripsy in most cases where other endoscopic treatment modalities have failed. Biliary stenting may be an alternative treatment option for frail and elderly patients or those with serious co morbidities. PMID:23345939

Background and study aims: Endoscopic sphincterotomy (EST) is effective, but recurrent bileduct stones are a common late complication. Because there are still no effective therapies for preventing this complication, some patients have experienced bileduct stone recurrence many times. We describe herein a method of abdominal massage to treat patients with prior cholecystectomy who have experienced recurrence of bileduct stones. PMID:27540575

An adolescent with depression treated with sertraline developed cholestasis and bileduct paucity, which resolved with medication discontinuation. Vanishing bileduct syndrome is an acquired destruction of interlobular bileducts. This type of drug-induced liver injury has been associated with other medications and requires practitioners' awareness of potential hepatotoxicity. PMID:26597434

Background Carcinoid tumors rarely arise in the extrahepatic bileduct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC) tumors in the distal bileduct (DBD) to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bileduct carcinoid tumors. Case presentation A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT) and magnetic resonance cholangiopancreaticography (MRCP) demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2nd portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size). The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. Conclusion Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bileduct. PMID:17227590

The technetium Tc 99m-labeled iminodiacetic acid cholescintigram is an extremely accurate examination for detecting early obstruction of the common bileduct in acutely ill patients suspected of having acute cholecystitis or possible obstruction days to years after cholecystectomy. The examination accurately detected common bileduct obstruction in 63 of 65 patients in these two diagnostic categories. Sonographic evaluations in 43 of these patients failed to reveal ductal dilatation or other abnormality in 26 cases, and was nondiagnostic because of overlying bowel gas in two cases. The success of the radionuclide examination is attributed to its ability to detect functional impedance to bile flow hours to days before anatomic ductal dilatation occurs, and occasionally even before the alkaline phosphatase level and other liver chemistry values suggest the presence of an obstruction.

Intraductal papillary neoplasm of the bileduct (IPNB) is a specific type of bileduct tumor. It has been proposed that it could be the biliary counterpart of the intraductal papillary neoplasm of the pancreas (IPMN-P). This hypothesis is supported by the presence of simultaneous intraductal tumors of both the bileduct and pancreas. There have been five reports of patients with simultaneous IPNB and IPMN-P. In all of these cases, biliary involvement was limited to the intrahepatic and perihilar bileduct, which had characteristics similar to IPMN-P and usually had slow progression in nature. Herein, we present the first case of extensive intraductal neoplasm involving the extrahepatic bileduct, intrahepatic bileduct, and entire length of the pancreas with a poor outcome, even after being treated aggressively with radical surgery and adjuvant chemotherapy. Additionally, we summarize previous case reports of simultaneous intraductal lesions of the bileduct and pancreas. PMID:26925284

In the last 5 years 25 patients (11 men, 14 women) with carcinoma of the extrahepatic biliary duct were studied. The most frequent localization of the carcinoma was the hepatic hilum. D.C.P. according to Whipple was possible only in one patient, while in 20 patients a palliative approach with external and internal biliary derivations was the choice. In the remaining 4 patients an explorative laparotomy with biopsy was performed. It is concluded that palliative resection allows for a better quality of life. PMID:9162182

Although the most common cause of cholecystitis is gallstones, other conditions may present as acute cholecystitis. We describe a case of eosinophilic cholecystitis with common bileduct stricture. A 36-year-old woman initially had generalised abdominal pain and peripheral eosinophilia. Diagnostic laparoscopy showed eosinophilic ascites and necrotic nodules on the posterior abdominal wall. She was treated with anthelminthics on presumption of toxacara infection based on borderline positivity of serological tests. She later presented with acute cholecystitis and had a cholecystectomy and choledocotomy. Day 9 T-tube cholangiogram showed irregular narrowing of the distal common bileduct. The patient's symptoms were improved with steroids and the T-tube was subsequently removed. PMID:27222280

Purpose There is still some debate on surgical procedures for hepatocellular carcinoma (HCC) patients with bileduct tumor thrombi (BDTT, Ueda type 3 or 4). What is adequate extent of liver resection for curative treatment? Is extrahepatic bileduct resection mandatory for cure? The aim of this study is to answer these questions. Methods Between February 1994 and December 2012, 877 consecutive HCC patients underwent hepatic resection at Ajou University Hospital. Thirty HCC patients (3.4%) with BDTT (Ueda type 3 or 4) were retrospective reviewed in this study. Results In total, 20 patients enrolled in this study were divided into 2 groups: patients who underwent hemihepatectomy with extrahepatic bileduct resection (group 1, n = 10) and with only removal of BDTT (group 2, n = 10). The 1-, 3- and 5-year overall survival rates were 75.0%, 50.0%, and 27.8%, respectively. The 1-, 3-, and 5-year survival rates of group 1 were 100.0%, 80.0%, and 45.7%, and those of group 2 were 50.0%, 20.0%, and 10.0%, respectively (P = 0.014). The 1-, 3-, and 5-year recurrences free survival rates of group 1 were 90.0%, 70.0%, and 42.0%, and those of group 2 were 36.0%, 36.0%, and 0%, respectively (P = 0.014). Thrombectomy and infiltrative growth type (Ig) were found as independent prognostic factors for recurrence free survival by multivariate analysis. Thrombectomy, Ig, and high indocyanine green retention rate at 15 minutes were found as independent prognostic factors for overall survival by multivariate analysis. Conclusion We suggest that the appropriate surgical procedure for icteric HCC patients should be comprised of ipsilateral hemihepatectomy with caudate lobectomy and extrahepatic bileduct resection. PMID:26942157

Cytosolic calcium (Cai(2+)) is a second messenger that is important for the regulation of secretion in many types of tissues. Bileduct epithelial cells, or cholangiocytes, are polarized epithelia that line the biliary tree in liver and are responsible for secretion of bicarbonate and other solutes into bile. Cai(2+) signaling plays an important role in the regulation of secretion by cholangiocytes, and this review discusses the machinery involved in the formation of Ca(2+) signals in cholangiocytes, along with the evidence that these signals regulate ductular secretion. Finally, this review discusses the evidence that impairments in cholangiocyte Ca(2+) signaling play a primary role in the pathogenesis of cholestatic disorders, in which hepatic bile secretion is impaired. PMID:24612866

Percutaneous transhepatic cholangiography (PTC) with subsequent external bile drainage by nonsurgically established percutaneous transhepatic intubation of bileducts was performed in 105 patients with obstructive jaundice. Recovery of liver function and improvement in the patients' general condition prior to radical or palliative surgery, nonsurgical palliation in advanced cases of malignancy as well as relief of postoperative leakage from a biliodigestive anastomosis are the indications for the bile drainage technique used in the present study. Clinical aspects such as optimal period of preoperative drainage, frequency of catheter dislodgement, and rate of complications such as cholangitis, bile leakage to the abdominal cavity and risk for peritoneal hemorrhage are discussed. Two deaths occurred within this series. PMID:758865

Endoscopic treatment for bileduct stones is low-invasive and currently considered as the first choice of the treatment. For the treatment of bileduct stones, papillary treatment is necessary, and the treatments used at the time are broadly classified into two types; endoscopic papillary balloon dilatation where bileduct closing part is dilated with a balloon and endoscopic sphincterotomy (EST) where bileduct closing part is incised. Both procedures have advantages and disadvantages. Golden standard is EST, however, there are patients with difficulty for EST, thus we must select the procedure based on understanding of the characteristics of the procedure, and patient backgrounds. PMID:27247706

Backgrounds/Aims In hepatocellular carcinoma (HCC), bileduct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bileduct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bileduct invasion, and assessed the clinical significance of bileduct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bileduct invasion on pathology. Patients with bileduct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bileduct invasion. In multivariate analysis, bileduct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bileduct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

Endoscopic treatment for bileduct stones is low-invasive and currently considered as the first choice of the treatment. For the treatment of bileduct stones, papillary treatment is necessary, and the treatments used at the time are broadly classified into two types; endoscopic papillary balloon dilatation where bileduct closing part is dilated with a balloon and endoscopic sphincterotomy (EST) where bileduct closing part is incised. Both procedures have advantages and disadvantages. Golden standard is EST, however, there are patients with difficulty for EST, thus we must select the procedure based on understanding of the characteristics of the procedure, and patient backgrounds. PMID:27247706

Synchronous double cancer of the common bileduct is exceptional and only one reported case was found in the literature. We report a case in which the diagnosis of the double tumor was missed by computed tomography scan, magnetic resonance imaging, and endoscopic ultrasonography. The diagnosis of the distal tumor was made only during surgery. There was no communication in either the mucosal layer or the subepithelial layer between the 2 cancers without periductal lymphatic spread, thus suggesting that they are primary. PMID:21167357

Background Studies have shown that the absence of bile in the gut lumen, either by bileduct ligation or bile diversion, induces mucosal injury. However, the mechanism remains elusive. In this study, the role of bile pigments in gut barrier function was investigated in a rat model of bileduct ligation. Methods Male Sprague Dawley (SD) rats were used in this study. After ligation of bileduct, the animals were administrated with free bilirubin, bilirubin ditaurate, or biliverdin by intragastric gavage. 1, 2, or 3 days later, the animals were sacrificed and the damage of mucosa was assessed by histological staining as well as biochemical parameters such as changes of diamine oxidase (DAO) and D-lactate (D-Lac) in the blood. Trypsin and chymotrypsin of the gut were also measured to determine how these digestive proteases may relate to the observed effects of bile pigments. Results Bileduct ligation (BDL) caused significant increases in gut trypsin and chymotrypsin along with damage of the mucosa as demonstrated by the histological findings under microscope, the reduced expression of tight junction molecules like occludin, and significant changes in DAO and D-lac in the blood. Free bilirubin but not bilirubin ditaurate or biliverdin showed significant inhibitions on trypsin and chymotrypsin as well as alleviated changes of histological and biochemical parameters related to gut barrier disruption. Conclusion Bile may protect the gut from damage through inhibiting digestive proteases like trypsin and chymotrypsin by free bilirubin. PMID:24892651

Since the advent of laparoscopic surgery of cholelithiasis the incidence rate of bileduct injuries has increased significantly in the literature in relation to the operators' learning curve. Unknown injuries can have dramatic, immediate consequences and progress to bile peritonitis. Moreover surgical repair of external biliary fistula at the stage of bileduct dilatation requires biliodigestive anastomosis or liver resections "réglées". PMID:27279975

Neuroendocrine carcinoma (NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma (cT4N1M0, cStage IV). He underwent a right hepatectomy combined with extrahepatic bileduct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis. PMID:27570432

The authors report six patients who had injuries to their common hepatic bileduct at laparoscopic cholecystectomy over a 16-month period. Five of the six complications could be attributed to laser injuries during dissection in the region of Calot's triangle. The authors discuss the possible mechanism of these injuries, their perioperative management, and the methods of surgical reconstruction. The follow-up period ranges from 3 months to 21 months. Liver function parameters and isotope biliary excretion scans are back to normal in all six patients. The potential hazards of laparoscopic surgery demand that extraordinary care be used not only during the actual surgical procedure, but also in the preoperative decision concerning the dissection method to be employed. Images FIG. 2. FIG. 3. FIG. 4. FIG. 5. FIG. 6. PMID:1531914

Introduction Perihilar cholangiocarcinoma is the most frequent cholangiocarcinoma and poses difficulties in preoperative evaluation. For its therapy, often major hepatic resections as well as resection and reconstruction of the hepatic artery or the portal vein are necessary. In the last decades, great advances were made in both the surgical procedures and the perioperative anesthetic management. In this article, we describe from our point of view which facts represent the limits for curative (R0) resection in perihilar cholangiocarcinoma. Methods Retrospective data of a 6-year period (2008-2014) was collected in an SPSS 22 database and further analyzed with focus on the surgical approach and the postoperative as well as histological results. Results Out of 96 patients in total we were able to intend a curative resection in 73 patients (76%). In 58/73 (79.5%) resections an R0 situation could be reached (R1 n = 14; R2 n = 1). 23 patients were irresectable because of peritoneal carcinosis (n = 8), broad infiltration of major blood vessels (n = 8), bilateral advanced tumor growth to the intrahepatic bileducts (n = 3), infiltration of the complete liver hilum (n = 2), infiltration of the gallbladder (n = 1), and liver cirrhosis (n = 1). Patients with a T4 stadium were treated with curative intention twice, and in each case an R1 resection was achieved. Most patients with irresectable tumors can be suspected to have a T4 stadium as well. In a T3 situation (n = 6) we could establish five R0 resections and one R1 resection. Conclusion The limit of surgical resection for bileduct cancer is the advanced tumor stage (T stadium). While in a T3 stadium an R0 resection is possible in most cases, we were not able to perform an R0 resection in a T4 stadium. From our point of view, early T stadium cannot usually be estimated through expanded diagnostics but only through surgical exploration. PMID:26468314

AIM: To describe our experience concerning the surgical treatment of Strasberg E-4 (Bismuth IV) bileduct injuries. METHODS: In an 18-year period, among 603 patients referred to our hospital for surgical treatment of complex bileduct injuries, 53 presented involvement of the hilar confluence classified as Strasberg E4 injuries. Imagenological studies, mainly magnetic resonance imaging showed a loss of confluence. The files of these patients were analyzed and general data were recorded, including type of operation and postoperative outcome with emphasis on postoperative cholangitis, liver function test and quality of life. The mean time of follow-up was of 55.9 ± 52.9 mo (median = 38.5, minimum = 2, maximum = 181.2). All other patients with Strasberg A, B, C, D, E1, E2, E3, or E5 biliary injuries were excluded from this study. RESULTS: Patients were divided in three groups: G1 (n = 21): Construction of neoconfluence + Roux-en-Y hepatojejunostomy. G2 (n = 26): Roux-en-Y portoenterostomy. G3 (n = 6): Double (right and left) Roux-en-Y hepatojejunostomy. Cholangitis was recorded in two patients in group 1, in 14 patients in group 2, and in one patient in group 3. All of them required transhepatic instrumentation of the anastomosis and six patients needed live transplantation. CONCLUSION: Loss of confluence represents a surgical challenge. There are several treatment options at different stages. Roux-en-Y bilioenteric anastomosis (neoconfluence, double-barrel anastomosis, portoenterostomy) is the treatment of choice, and when it is technically possible, building of a neoconfluence has better outcomes. When liver cirrhosis is shown, liver transplantation is the best choice. PMID:26527428

Over the course of the last several years hyperspectral imaging (HSI) has seen increased usage in biomedicine. Within the medical field in particular HSI has been recognized as having the potential to make an immediate impact by reducing the risks and complications associated with laparotomies (surgical procedures involving large incisions into the abdominal wall) and related procedures. There are several ongoing studies focused on such applications. Hyperspectral images were acquired during pancreatoduodenectomies (commonly referred to as Whipple procedures), a surgical procedure done to remove cancerous tumors involving the pancreas and gallbladder. As a result of the complexity of the local anatomy, identifying where the common bileduct (CBD) is can be difficult, resulting in comparatively high incidents of injury to the CBD and associated complications. It is here that HSI has the potential to help reduce the risk of such events from happening. Because the bile contained within the CBD exhibits a unique spectral signature, we are able to utilize HSI segmentation algorithms to help in identifying where the CBD is. In the work presented here we discuss approaches to this segmentation problem and present the results.

Background: Cognitive functions are impaired in patients with liver disease. Bileduct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Methods: Cholestasis was induced in male Wistar rats by ligating the main bileduct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bileduct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. Results: The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P < 0.05) impaired at day 21 post-bileduct ligation compared with the results for the control group. Additionally, memory was significantly impaired on day 7 (P < 0.01), day 14, and day 21 (P < 0.001) compared with the control groups. The levels of total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, and alkaline phosphatase were significantly higher at day 7, day 14, and day 21 post-bileduct ligation compared with the levels in the sham group. Conclusion: Based on these findings, both liver and memory function were affected in the early stage of cholestasis (7 days after bileduct ligation), while learning and locomotor activity were impaired at 21 days after bileduct ligation following the progression of cholestasis. PMID:24639608

Background: Liver transplantation has become the treatment of choice for patients with end-stage acute or chronic hepatic disease. Bileduct complications are common events after liver transplantation. The aim of this study was to evaluate the blood supply of the human bileduct and identify the underlying mechanisms of bileduct complications after liver transplantation. Methods: The duct supply branches from gastroduodenal artery and blood supply of extrahepatic bileduct system were re-evaluated through selective hepatic angiography from 600 patients. In addition, 33 cadavers were injected with latex casting material into the common hepatic artery, then the extrahepatic bileduct and the branches from the common hepatic artery were carefully dissected to visualize the gastroduodenal artery and its branching to the extrahepatic bileduct. Results: The bileduct artery arose from the branch of the gastroduodenal artery in 8.1% (49/600). Of these 49 individuals, the bileduct artery was supplied by the gastroduodenal artery (61.22%, 30/49), the proper hepatic artery (14.29%, 7/49), or both the gastroduodenal artery and the proper hepatic artery (24.49%, 12/49). In our study of 33 cadavers, the percentage that the bileduct artery arose from the gastroduodenal artery was 27.27%. The blood supply to the bile extrahepatic bileducts was divided into different segments and formed longitudinal and arterial network anastomosed on the walls of the duct. Conclusions: There is a close relationship between the duct supply branches from gastroduodenal artery and the blood supplying patterns of the extrahepatic bileduct system. In liver transplant surgery, the initial part of the gastroduodenal artery is preferred to be preserved in the donor liver. It is of great significance to improve the success rate of operation and reduce complications. PMID:25635427

Hepatobiliary scintigraphy performed in a patient suspected of having common bileduct obstruction showed persistence of the hepatic parenchymal phase and no bileduct or gallbladder activity during the first hour of imaging. On endoscopic retrograde cholangiopancreatography examination several hours later, an obstructing gallstone was identified in the common bileduct, and the stone was extracted in conjunction with a papillotomy. Delayed scintigraphic images at 6 hours were unchanged from the earlier views, but imaging at 24 hours showed tracer activity in the small bowel and colon along with persistent hepatic parenchymal activity. These results demonstrate that hepatobiliary radiopharmaceuticals remain in an excretable form in the liver in patients with complete common duct obstruction, but that resumption of bile flow and tracer excretion does not occur until a number of hours after relief of the obstruction. PMID:8616993

A common bileduct perforation due to sphincteroplasty is reported. It was managed by temporary insertion of a metal fully covered stent with good outcomes. Images from the procedure are provided. PMID:27554382

A 35 years old lady presented with fever, biliary colic, mild jaundice, indigestion and flatulence. The upper abdominal ultrasonography revealed cholecystitis with sludge and a round worm in the common bileduct. Laparoscopic cholecystectomy and exploration of the bileduct for the removal of round worm was performed. The post-operative period was uneventful and the patient was discharged fit on the 4th post-operative day. PMID:17542295

The purpose of this study was to determine the primary patency of two or more noncoaxial self-expanding metallic Wallstents (Boston Scientific, Natick, MA) and to compare this with the primary patency of a single stent in malignant bileduct obstruction. From August 2002 to August 2004, 127 patients had stents placed for malignant bileduct obstruction. Forty-five patients were treated with more than one noncoaxial self-expanding metallic stents and 82 patients had a single stent placed. Two patients in the multiple-stent group were lost to follow-up. The primary patency period was calculated from the date of stenting until the first poststenting intervention for stent occlusion, death, or the time of last documented follow-up. The patency of a single stent was significantly different from that of multiple stents (P = 0.0004). In the subset of patients with high bileduct obstruction, the patency of a single stent remained significantly different from that of multiple stents (P = 0.02). In the single-stent group, there was no difference in patency between patients with high vs. those with low bileduct obstruction (P = 0.43). The overall median patency for the multistent group and the single-stent group was 201 and 261 days, respectively. In conclusion, the patency of a single stent placed for malignant low or high bileduct obstruction is similar, and significantly longer than, that of multiple stents placed for malignant high bileduct obstruction. Given the median patency of 201 days, when indicated, percutaneous stenting of multiple bileducts is an effective palliative measure for patients with malignant high bileduct obstruction.

Imaging of common bileduct (CBD) can be done by many techniques. Endoscopic retrograde cholangiopancreaticography is considered the gold standard for imaging of CBD. A standard technique of imaging of CBD by endoscopic ultrasound (EUS) has not been specifically described. The available descriptions mention different stations of imaging from the stomach and duodenum. The CBD lies closest to duodenum and choice of imaging may be restricted to duodenum for many operators. Generally most operators prefer multi station imaging during EUS and the choice of selecting the initial station varies from operator to operator. Detailed evaluation of CBD is frequently the main focus of imaging during EUS and in such situations multi station imaging with a high-resolution ultrasound scanner may provide useful information. Examination of the CBD is one of the primary indications for doing an EUS and it can be done from five stations: (1) the fundus of stomach; (2) body of stomach; (3) duodenal bulb; (4) descending duodenum; and (5) antrum. Following down the upper 1/3rd of CBD can do imaging of entire CBD from the liver window and following up the lower 1/3rd of CBD can do imaging of entire CBD from the pancreatic window. This article aims at simplifying the techniques of imaging of CBD by linear EUS. PMID:26504506

Bileduct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL. PMID:27556445

There are two major hurdles to carrying out endoscopic retrograde cholangiopancreatography (ERCP) in patients with altered gastrointestinal anatomy (Billroth II gastrectomy [B-II], Roux-en-Y anastomosis [R-Y] etc.), post-pancreatoduodenectomy or post-choledochojejunostomy. These are: (i) the endoscopic approach to the afferent loop, blind end, and the site of bilio-pancreatic anastomosis; and (ii) bileduct and/or pancreatic duct cannulation. Balloon-assisted enteroscopy (BAE) became available in recent years and is now being actively used to overcome the first hurdle and, at least, the success rate has improved. However, room for improvement still remains in regards to the second hurdle (i.e. the success rate of cannulation of the bileduct and/or pancreatic duct), and there has been a desire for the development of dedicated devices (ERCP catheters, hoods etc.) and for improvement in the functionality of the enteroscopes etc. In the present review, we explain the basic procedure for bileduct and/or pancreatic duct cannulation with conventional endoscopes and BAE, and modifications of the basic procedure. PMID:24750161

Despite advances in speciality care, mortality and morbidity remain the most important issues in the management of post-cholecystectomy bileduct injuries. We analysed the peri-operative management of post-cholecystectomy bileduct injuries to assess their outcomes. Of 150 patients with post-cholecystectomy bileduct injuries, 13 patients who presented with strictured hepaticojejunostomy were excluded from the analysis. The records of the remaining 137 patients were analysed for type of presentation, management and follow-up. Of 137 injuries, 88 were open and 49 were laparoscopic. Various presentations include acute bileduct injury (n = 5), bile collection (n = 45), external biliary fistula (n = 46) and stricture (n = 41). After initial management, three patients died (sepsis, n = 2; pseudoaneurysmal bleed, n = 1). Of 107 patients who underwent definitive repair, three died (portal hypertension, n = 2; sepsis, n = 1). At median follow-up of 30 months, 100 patients had good outcome (grade A, B), and only 4 had bad outcome (grade C, D) as per McDonald grading. Peritonitis and sepsis in the early phase and portal hypertension and cirrhosis in the late phase are the main causes of mortality in patients sustaining bileduct injury during cholecystectomy. Successful management in a specialist hepatobiliary centre can limit the morbidity in more than 90 % cases. PMID:26730060

Background. Spontaneous perforation of the extrahepatic biliary system is a rare presentation of gall stones. Very few cases of bileduct perforation have been reported in adults. It is rarely suspected or correctly diagnosed preoperatively. Case Presentation. A 66-year-old female presented at the surgical emergency with 3 days' history of severe upper abdominal pain with distension and repeated episodes of vomiting, as she had evidence of generalized peritonitis and underwent an exploratory laparotomy. A single 0.5 cm × 0.5 cm free perforation was present on the anterolateral surface of the common bileduct at the junction of cystic duct. A cholecystectomy and the CBD exploration were performed. Conclusion. Spontaneous perforation of the extrahepatic bileduct is a rare but important presentation of gall stones in adults. Therefore, awareness of the clinical presentation, expert ultrasound examination, and surgery are important aspects in the management. PMID:27433361

Bileduct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bileducts. The aim of this study was to determine the impact of NMP on bileduct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bileduct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bileducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bileduct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. PMID:26946466

We determined the mechanisms of hepatobiliary injury in the lithocholic acid (LCA)-fed mouse, an increasingly used model of cholestatic liver injury. Swiss albino mice received control diet or 1% (w/w) LCA diet (for 1, 2, and 4 days), followed by assessment of liver morphology and ultrastructure, tight junctions, markers of fibrosis and key proteins of hepatobiliary function, and bile flow and composition. As expected LCA feeding led to bile infarcts, which were followed by a destructive cholangitis with activation and proliferation of periductal myofibroblasts. At the ultrastructural level, small bileducts were frequently obstructed by crystals. Biliary-excreted fluorescence-labeled ursodeoxycholic acid accumulated in bile infarcts, whereas most infarcts did not stain with India ink injected into the common bileduct; both findings are indicative of partial biliary obstruction. Expression of the main basolateral bile acid uptake proteins (sodium-taurocholate cotransporter and organic anion-transporting polypeptide 1) was reduced, the canalicular transporters bile salt export pump and multidrug-related protein 2 were preserved, and the basolateral transporter multidrug-related protein 3 and the detoxifying enzyme sulfotransferase 2a1 were induced. Thus, we demonstrate that LCA feeding in mice leads to segmental bileduct obstruction, destructive cholangitis, periductal fibrosis, and an adaptive transporter and metabolic enzyme response. PMID:16436656

Abstract To evaluate the clinical and technical factors affecting the ability of fluorescence cholangiography (FC) using indocyanine green (ICG) to delineate the bileduct anatomy during laparoscopic cholecystectomy (LC). Application of FC during LC began after laparoscopic fluorescence imaging systems became commercially available. In 108 patients undergoing LC, FC was performed by preoperative intravenous injection of ICG (2.5 mg) during dissection of Calot's triangle, and clinical factors affecting the ability of FC to delineate the extrahepatic bileducts were evaluated. Equipment-related factors associated with bileduct detectability were also assessed among 5 laparoscopic systems and 1 open fluorescence imaging system in ex vivo studies. FC delineated the confluence between the cystic duct and common hepatic duct (CyD–CHD) before and after dissection of Calot's triangle in 80 patients (74%) and 99 patients (92%), respectively. The interval between ICG injection and FC before dissection of Calot's triangle was significantly longer in the 80 patients in whom the CyD–CHD confluence was detected by fluorescence imaging before dissection (median, 90 min; range, 15–165 min) than in the remaining 28 patients in whom the confluence was undetectable (median, 47 min; range, 21–205 min; P bile duct samples was significantly different among the laparoscopic imaging systems and tended to decrease more steeply than those of the open imaging system as the target-laparoscope distance increased and porcine tissues covering the samples became thicker. FC is a simple navigation tool for obtaining a biliary roadmap to reach the “critical view of safety” during LC. Key factors for better bileduct identification by FC are administration of ICG as far in advance as possible before surgery, sufficient extension of connective tissues around the bileducts, and placement of the tip of

Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bileduct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bileduct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bileduct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bileduct hyperplasia. Images Figure 1 Figure 3 PMID:6147091

Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bileduct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bileduct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bileduct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bileduct hyperplasia. PMID:6147091

Magnetic compression anastomosis (MCA) provides a minimally invasive treatment creating a nonsurgical, sutureless enteric anastomosis in conjunction with an interventional radiologic technique by using 2 high-power magnets. Recently, the MCA technique has been applied to bileduct strictures after living donor liver transplantation or major hepatectomy. Herein we described use of MCA for bileduct stenosis 5 months after donor left hepatectomy in a 24-year-old man who presented with a stricture at the porta hepatis and intrahepatic bileduct dilatation. Unsuccessful transpapillary biliary drainage and balloon dilatation through a percutaneous transhepatic biliary drainage (PTBD) route led to the MCA. A 4-mm-diameter cylindrical samarium-cobalt (Sm-Co) daughter magnet with a long nylon wire was placed at the superior site of the obstruction through the PTBD route. A 5-mm-diameter Sm-Co parent magnet with an attached nylon handle was endoscopically inserted into the common bileduct and placed at the inferior site of obstruction. The 2 magnets were attracted, sandwiching the stricture and establishing a reanastomosis. In conclusion, the MCA technique was a unique procedure for choledochocholedochostomy in a patient with bileduct stenosis after donor hepatectomy. PMID:22483501

AIM: To examine the usefulness of a new tapered metallic stent (MS) in patients with unresectable malignant hilar bileduct obstruction. METHODS: This new tapered MS was placed in 11 patients with Bismuth II or severer unresectable malignant hilar bileduct obstruction, as a prospective study. The subjects were six patients with bileduct carcinoma, three with gallbladder cancer, and two with metastatic bileduct obstruction. Stenosis morphology was Bismuth II: 7, IIIa: 3, and IV: 1. UMIN Clinical Trial Registry (UMIN000004758). RESULTS: MS placement was 100% (11/11) successful. There were no procedural accidents. The mean patency period was 208.401 d, the median survival period was 142.000 d, and the mean survival period was 193.273 d. Occlusion rate was 36.4% (4/11); the causes of occlusion were ingrowth and overgrowth in 2 patients each, 18.2%, respectively. Patients with occlusion underwent endoscopic treatment one more time and all were treatable. CONCLUSION: The tapered MS proved useful in patients with unresectable malignant hilar bileduct obstruction because it provided a long patency period, enabled re-treatment by re-intervention, and no procedural accidents occurred. PMID:26488025

Cattle grazing turnips or other brassica forage crops occasionally develop hepatogenous photosensitization. In New Zealand, cases of bovine photosensitization associated with such crops frequently occur during late summer and fall, and this coincides with the facial eczema (sporidesmin toxicosis) "season." Clinical chemistry findings in acute photosensitization cases associated with both brassica and facial eczema include marked serum elevations in γ-glutamyl transferase and glutamate dehydrogenase activities. Distinctive bileduct lesions of "subacute" turnip photosensitization in 2 cows, comprising microscopic cholangiectasis with concentric periductal fibrosis of small bileducts, and a spectrum of changes from bileduct necrosis progressing to obliterative sclerosis are described. These bileduct lesions are compared with those in 3 cases of "subacute" facial eczema in adult cows, where medium-sized and larger ducts tend to be involved and bileduct hyperplasia and portal fibrosis are more prominent, often leading to bridging between neighboring portal triads. PMID:24280939

Congenital absence of the common bileduct (CBD) is an extremely rare developmental anomaly with right and left hepatic ducts draining directly into the gallbladder (GB). Other synonyms for this clinical condition are "cholecystohepatic ducts", "transverse lie of the GB" or "interposition of the GB". The potential for iatrogenic injury is high, because of either inadvertent division or ligation of the ducts. Diagnosis is mostly made intraoperatively, and needs some form of biliary reconstruction. Herein, we are reporting a case of congenital absence of the CBD in a 36-year-old lady that was detected intraoperatively. PMID:27279403

Background The preoperative diagnosis of biliary stenosis is associated with low accuracy. As a consequence, probe-based confocal laser endomicroscopy (pCLE), an in-vivo histological imaging technique, was applied in the bileduct. The aim of this study was to establish whether previous inflammation of the bileduct affects confocal interpretation. The findings from pCLE were compared in two groups of patients: those in whom there had been no cholangitis nor stenting and those in whom stents had been used and subsequently retrieved or who had suffered cholangitis. Patients and methods pCLE was performed on 54 patients (mean age 66 years; 31 men, 23 women) from September 2008 to July 2011. Patients were divided in two groups: group 1: 39 patients who had not undergone a biliary procedure in the month preceding the pCLE procedure; and group 2: 15 patients who had undergone stent placement or presented with cholangitis in the month preceding the pCLE procedure. Endoscopic and pCLE data were collected prospectively. pCLE results were compared to benchmark histology (surgery, endoultrasonography, percutaneous biopsy). Patients with a benign stricture who did not undergo operation were followed for 1 year. pCLE images of the bileduct were obtained during endoscopic retrograde cholangiopancreatography procedures. pCLE images were interpreted prospectively using the Miami classification in vivo and in real time. Results In group 1, sensitivity, specificity, and accuracy were 88, 83, and 87%, respectively. In group 2, sensitivity, specificity, and accuracy were 75, 71, and 73%, respectively. Diagnostic accuracy of pCLE was lower when applied to group 2 (p bile ducts affected by inflammation from cholangitis or previous stenting. Conclusions Inflammatory lesions of the bileduct interfere with interpretation of pCLE. A refined pCLE description of inflammatory lesions should improve accuracy of pCLE in bileduct stenosis

A new type of endoscopic surgery (magnetic cholecystodigestive anastomoses) is presented as an alternative to conventional palliative treatment of mechanical obstruction with icterus located below the bileduct inlet. By means of endoscopic technique, two clinically usable methods of creating delayed magnetic cholecystogastric anastomoses and one modality of implanting cholecystoenteric and enteroenteric anastomosis have been worked out in the experiment conducted on 50 mongrels with mechanical icterus. Ring-shaped or rectangular magnets were implanted in the gallbladder through laparoscopic cholecystostomy. Implantation into the stomach was accompanied by simultaneous gastroscopy. In clinical conditions, four endoscopic cholecystogastric anastomoses and one cholecystoduodenal anastomosis have been performed on patients suffering from malignant obstruction of distal bileduct due to cancer of the head of the pancreas, making any radical surgery pointless. The preliminary results indicate that endoscopic magnetic cholecystodigestive anastomoses can serve as a form of palliative treatment of distal bileduct malignant obstructions. PMID:7686058

Palliative treatment of obstructive jaundice with the help of biliary endoprosthesis due to the possible complication of post-intervention in the form of insolvency stent deformation or dislocation. The study features in the postoperative period of the main bileduct endoprosthesis about their two-component unit, described the syndrome of the closed space of the bileducts. On the basis of observation of 14 patients with the given anatomical feature of endoscopic, who were underwent stenting, was assessed frequency of the syndrome and possibilities of its prevention. Interstenosis space expansion of the main bileduct can be a reason for local cholangitis. For the prevention of cholangitis, it should be carried out a separate drainage of interstenosis space with the help of endoprosthesis or by proximal supra-stenotic extension of two or more stents. PMID:27263209

Despite best efforts, bileduct injury during laparoscopic cholecystectomy is a major potential complication. Precise detection method of extrahepatic bileduct during laparoscopic procedures would minimize the risk of injury. Towards this goal, we have developed a compact imaging instrumentation designed to enable simultaneous acquisition of conventional white color and NIR fluorescence endoscopic/laparoscopic imaging using ICG as contrast agent. The capabilities of this system, which offers optimized sensitivity and functionality, are demonstrated for the detection of the bileduct in an animal model. This design could also provide a low-cost real-time surgical navigation capability to enhance the efficacy of a variety of other image-guided minimally invasive procedures.

Temozolomide, an oral alkylating agent, is used in the treatment of glioblastoma. We describe a case of a 62-year-old woman developing jaundice with significant derangement of liver function tests on day 17 of focal radiotherapy with concomitant temozolomide. There was no structural abnormality on imaging and liver biopsy was performed. Pathology revealed absence of small terminal bileducts affecting up to 60% of sampled portal tracts and senescence of many of the remaining small bileducts, in keeping with a diagnosis of acute vanishing bileduct syndrome. This is a rare syndrome. It has been documented in association with Hodgkin's lymphoma and viral causes. Drugs implicated as precipitating this condition include antiseizure medications, some antibiotics, ibuprofen and antifungals. Temozolomide was stopped. The patient received supportive care, ursodeoxycholic acid 750 mg daily and cholestyramine 4 g twice daily. She was otherwise asymptomatic and her blood results returned to normal by day 129. PMID:25432915

Laparoscopic cholecystectomy is one of the most commonly performed operations worldwide. Cystic duct is the most common site of bile leak after cholecystectomy. The treatment of choice is usually conservative. Using sufficient percutaneous drainage of the biloma cavity and endoscopic retrograde cholangiography (ERCP) with sphincterotomy and/or stenting, the cure rate of bile leaks is greater than 90%. In very rare cases, all of these measures remain unsuccessful. We report a technique for the successful treatment of persistent cystic duct leak. After failed ERCP and stenting, bile leak was treated by coiling the cystic duct through a drain tract. This technique is safe and effective and helps avoid the morbidity of reoperation. PMID:26798539

Since diseases of the liver and bileducts are common, a clinician is faced by the need to implement an appropriate diagnostic process. It is necessary to apply diagnostic methods that enable appropriate assessment of the most common pathologies of the liver, i.e. fibrosis, steatosis and focal lesions, as well as initial assessment of the bileducts. These goals can be achieved using ultrasound methods based on conventional sonography, contrast-enhanced sonography and elastography. The assessment of fatty liver and bileduct dilatation using ultrasound reaches satisfactory levels of sensitivity and specificity. The usage of contrast agents enables unambiguous differentiation between benign and malignant focal lesions, frequently allowing them to be identified accurately without the assistance of other imaging modalities. Elastography has enabled reliable assessment of liver fibrosis. Its results are comparable to those of the standard method, i.e. liver biopsy. PMID:26673784

Purpose: This study was designed to clarify the advantages of biodegradable stents in terms of mucosal reaction and biodegradation after placement. We designed a biodegradable stent and assessed stent degradation and changes in the normal bileducts of dogs. Methods: The biodegradable stent is a balloon-expandable Z stent consisting of poly-l-lactic acid (PLLA) with a diameter of 6 mm and a length of 15 mm. We assessed four groups of three beagle dogs each at 1, 3, 6, and 9 months of follow-up. After evaluating stent migration by radiography and stent and bileduct patency by cholangiography, the dogs were sacrificed to remove the bileduct together with the stent. The bileduct lumen was examined macroscopically and histologically, and the stent degradation was examined macroscopically and by scanning electron microscopy (SEM). Results: Bileduct obstruction was absent and none of the stents migrated. Macroscopic evaluation showed moderate endothelial proliferation in the bileducts at the implant sites at 3 and 6 months and a slight change at 9 months. Slight mononuclear cell infiltration was histologically identified at all time points and epithelial hyperplasia that was moderate at 3 months was reduced to slight at 6 and 9 months. Stent degradation was macroscopically evident in all animals at 9 months and was proven by SEM in two dogs at 6 months and in all of them at 9 months. Conclusions: Our results suggest that PLLA bioabsorbable stents seems to be useful for implantation in the biliary system with further investigation.

Neuroendocrine carcinoma (NEC) of the extrahepatic bileduct is rare, and only 22 cases have been reported. Only two of these were large-cell NEC (LCNEC); the vast majority were small-cell NEC. Here, we report a third case of LCNEC of the extrahepatic bileduct. A 76-year-old male presented to a local hospital with painless jaundice. Imaging studies revealed a tumor at the hepatic hilum. The patient underwent right hepatic lobectomy, bileduct resection, and cholecystectomy. The resection specimen showed a 5.0-cm invasive neoplasm involving the hilar bileducts and surrounding soft tissue. Histologically, the tumor consisted of nests of medium to large cells with little intervening stroma. The tumor invaded a large portal vein branch. All four excised lymph nodes were positive for metastasis, and metastatic deposits were also present in the gallbladder wall. The tumor was diffusely positive for synaptophysin and focally positive for chromogranin A. Approximately 70%-80% of the tumor cells were positive for Ki-67, indicating strong proliferative activity. A diagnosis of LCNEC was made. A few bileducts within and adjacent to the invasive tumor showed dysplasia of the intestinal phenotype and were focally positive for synaptophysin and chromogranin A, suggesting that the dysplastic intestinal-type epithelium played a precursor role in this case. A postoperative computer tomography scan revealed rapid enlargement of the abdominal and retroperitoneal lymph nodes. The patient died 21 d after the operation. NEC of the bileduct is an aggressive neoplasm, and its biological characteristics remain to be better defined. PMID:23901240

Background. The management of choledocholithiasis has evolved from open common bileduct exploration (OCBDE) to therapeutic endoscopic retrograde cholangiopancreatography (ERCP) to laparoscopic common bileduct exploration (LCBDE). Each entails a degree of difficulty. Aim. To review 5-year results of bileduct exploration in an UGI unit. Methods. Common bileduct explorations (CBDEs) performed between January 2008 and January 2013 were identified from a prospectively collected clinical audit system and results reviewed retrospectively. Results. 216 CBDEs were performed, 119 (55%) as an emergency and 52 (24%) following failed ERCP. Open CBDE (OCBDE) was performed primarily in 34/216 (16%) patients and attempted laparoscopically in 182 (84%). Fifty nine (32%) Laparoscopic CBDEs (LCBDEs) were converted to OCBDE. Of the remaining 123 LCBDEs, 51 (41%) primary choledochotomies and 72 (59%) primary transcystic CBDEs (TC-CBDEs) were performed. Forty nine (68%) TC-CBDEs were considered successful and 23 (32%) failed. Fifteen failed TC-CBDEs were converted to a successful laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87%) patients and retained stones were identified in 20/123 (16%) LCBDEs. Complications occurred in 52/216 (24%) patients. There were 8/216 (4%) bile leaks requiring further intervention. Postoperative ERCP was carried out in 32/216 (15%) patients and 9/216 (4%) required relaparoscopy/laparotomy. No patient died. Conclusions. Successful management of choledocholithiasis requires a breadth of laparoscopic and endoscopic expertise. PMID:26420916

Background. The management of choledocholithiasis has evolved from open common bileduct exploration (OCBDE) to therapeutic endoscopic retrograde cholangiopancreatography (ERCP) to laparoscopic common bileduct exploration (LCBDE). Each entails a degree of difficulty. Aim. To review 5-year results of bileduct exploration in an UGI unit. Methods. Common bileduct explorations (CBDEs) performed between January 2008 and January 2013 were identified from a prospectively collected clinical audit system and results reviewed retrospectively. Results. 216 CBDEs were performed, 119 (55%) as an emergency and 52 (24%) following failed ERCP. Open CBDE (OCBDE) was performed primarily in 34/216 (16%) patients and attempted laparoscopically in 182 (84%). Fifty nine (32%) Laparoscopic CBDEs (LCBDEs) were converted to OCBDE. Of the remaining 123 LCBDEs, 51 (41%) primary choledochotomies and 72 (59%) primary transcystic CBDEs (TC-CBDEs) were performed. Forty nine (68%) TC-CBDEs were considered successful and 23 (32%) failed. Fifteen failed TC-CBDEs were converted to a successful laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87%) patients and retained stones were identified in 20/123 (16%) LCBDEs. Complications occurred in 52/216 (24%) patients. There were 8/216 (4%) bile leaks requiring further intervention. Postoperative ERCP was carried out in 32/216 (15%) patients and 9/216 (4%) required relaparoscopy/laparotomy. No patient died. Conclusions. Successful management of choledocholithiasis requires a breadth of laparoscopic and endoscopic expertise. PMID:26420916

The purpose of this study was to evaluate the clinical course of main bileduct stricture at the hepatic hilum after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Among 446 consecutive patients with HCC treated by TACE, main bileduct stricture developed in 18 (4.0%). All imaging and laboratory data, treatment course, and outcomes were retrospectively analyzed. All patients had 1 to 2 tumors measuring 10 to 100 mm in diameter (mean {+-} SD 24.5 {+-} 5.4 mm) near the hepatic hilum fed by the caudate arterial branch (A1) and/or medial segmental artery (A4) of the liver. During the TACE procedure that caused bileduct injury, A1 was embolized in 8, A4 was embolized in 5, and both were embolized in 5 patients. Nine patients (50.0%) had a history of TACE in either A1 or A4. Iodized oil accumulation in the bileduct wall was seen in all patients on computed tomography obtained 1 week later. Bileduct dilatation caused by main bileduct stricture developed in both lobes (n = 9), in the right lobe (n = 3), in the left lobe (n = 4), in segment (S) 2 (n = 1), and in S3 (n = 1). Serum levels of alkaline phosphatase and {gamma}-glutamyltranspeptidase increased in 13 patients. Biloma requiring drainage developed in 2 patients; jaundice developed in 4 patients; and metallic stents were placed in 3 patients. Complications after additional TACE sessions, including biloma (n = 3) and/or jaundice (n = 5), occurred in 7 patients and were treated by additional intervention, including metallic stent placement in 2 patients. After initial TACE of A1 and/or A4, 8 patients (44.4%), including 5 with uncontrollable jaundice or cholangitis, died at 37.9 {+-} 34.9 months after TACE, and 10 (55.6%) have survived for 38.4 {+-} 37.9 months. Selective TACE of A1 and/or A4 carries a risk of main bileduct stricture at the hepatic hilum. Biloma and jaundice are serious complications associated with bileduct strictures.

Laparoscopic hepatectomy has been widely performed for patients with benign liver tumors such as hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma.We here present a case of a 78-year-old female patient who was initially admitted to our department due to fever and jaundice for 2 days. Abdominal enhanced computed tomography scan showed intrahepatic and extrahepatic bileduct dilatation with liver atrophy of left lobe. Unenhanced nodules were seen within the left intrahepatic bileduct. Ultrasonography revealed intrahepatic and extrahepatic bileduct dilatation with viscous fluid, tubular adenoma? Tumor markers including alpha fetoprotein, carcinoembryonic antigen, and CA19-9 were normal. Preoperative total bilirubin was 64.4 mmol/L.Laparoscopic anatomical left hepatectomy and common bileduct exploration were performed. In this procedure, a lot of mucus was seen within the common bileduct and left intrahepatic bileduct. No bileduct stones were found after the exploration. During parenchymal transection, intraoperative hemorrhage from middle hepatic vein was met, and we repaired middle hepatic vein by laparoscopic suture (5-0 Prolene). No air embolism and hypotension were met. This operation took 232 minutes and estimated blood loss was 300 mL. Postoperative ultrasonography indicated a normal outflow of middle hepatic vein and there was no stricture. The patient's postoperative course was uneventful and was discharged on the 6th day after surgery. Postoperative pathological diagnosis was intrahepatic bileduct papillary mucinous cystadenoma. PMID:26871845

Secure reconstruction of multiple hepatic ducts severely damaged by tumor invasion or iatrogenic injury is very difficult. If percutaneous or endoscopic biliary stenting fails, one or more percutaneous transhepatic biliary drainage (PTBD) tubes must be maintained in place for the rest of the patient's life. To cope with such difficult situations, we present a surgical technique termed cluster hepaticojejunostomy (HJ), which can be coupled with palliative bileduct resection. The cluster HJ technique consisted of applying multiple internal biliary stents and a single wide porto-enterostomy to surrounding connective tissues. We present a preliminary study with six patients. Five perihilar cholangiocarcinoma patients undergoing palliative bileduct resection received this procedure. Follow-up PTBD tubogram and hepatobiliary scintigraphy were performed at 1-2 weeks after surgery, after which the PTBD tubes were removed. No patient showed surgical complications, and the 6-month patency rate of clustered HJ was 80%. Another patient with laparoscopic cholecystectomy-associated major bileduct injury showed no biliary complications in the 5-year period following this procedure. Based on the results of this study, the cluster HJ technique may be a useful surgical method enabling the secure reconstruction of severely damaged hilar bileducts. PMID:25956723

The presence of bile in the peritoneal cavity and obstructive jaundice without liver derangement in the neonatal period is pathognomonic of spontaneous perforation of the bile-ducts. These features can be demonstrated preoperatively with ultrasound, nuclide imaging and liver function tests, without recourse to paracentesis, and the risk of contaminating the bile ascites. Furthermore, the presence of isotope in the general peritoneal cavity will exclude the diagnosis of a choledochal cyst so that jejunum should not be anastamosed to the 'false capsule' of a spontaneous perforation. PMID:3067698

A 45-year-old woman with advanced gastric carcinoma presented with obstructive jaundice. Percutaneous transhepatic cholangiography (PTC) revealed erosive disruption of the extrahepatic bileducts by a cavitating metastasis in the porta hepatis, as well as a biliary-duodenal fistula. External-internal biliary drainage via the fistula was plagued by recurrent drain occlusion by necrotic debris. This was ultimately alleviated by successful catheterization of the distal common bileduct (CBD) through the cavity, and linking the common hepatic duct (CHD) and CBD with a Wallstent, across the cavity. This succeeded in improving internal biliary drainage and isolating the exfoliating debris of the cavity from the bileducts.

AIM: To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bileduct (IPMN-B). METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented. RESULTS: Conventional imaging showed diffuse dilatation of bileducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bileducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bileducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bileducts in invasive cases. PMID:26167082

We investigated the immunoexpression of the intermediate filament proteins, cytokeratin and desmin, and the morphological changes in the liver of rats during experimental fasciolosis at 4, 7 and 10 weeks post-infection. Rats were infected with 30 Fasciola hepatica metacercariae. Paraffin sections of the liver were stained using H & E, PAS and azan stains. Immunohistochemical reactions were performed using antibodies against cytokeratin and desmin. The experimental F. hepatica infection led to fibrosis and cirrhosis of the liver, and to inflammation of the common bileducts. The expression of cytokeratin was increased in the epithelial cells of both the liver bile ductules at 4, 7 and 10 weeks post-infection and in the common bileducts at 7 and 10 weeks post-infection compared to uninfected rats; expression in the common bileducts was more intense. The myofibroblasts of the liver and smooth myocytes of the interlobular bileducts and common bileducts, showed a slight increase in desmin expression compared to the uninfected rats. The increased expression of cytokeratins in the hyperplastic rat common bileduct epithelium during the biliary phase of fasciolosis at 7 and 10 weeks post-infection may be explained by mechanical irritation by the parasite and an inflammatory reaction in the bileduct epithelium and in periductal fibrous tissue. PMID:25923046

Congenital absence of the common bileduct (CBD) is an extremely rare developmental anomaly with right and left hepatic ducts draining directly into the gallbladder (GB). Other synonyms for this clinical condition are “cholecystohepatic ducts”, “transverse lie of the GB” or “interposition of the GB”. The potential for iatrogenic injury is high, because of either inadvertent division or ligation of the ducts. Diagnosis is mostly made intraoperatively, and needs some form of biliary reconstruction. Herein, we are reporting a case of congenital absence of the CBD in a 36-year-old lady that was detected intraoperatively. PMID:27279403

We present the first case of an intraductal papillary neoplasm of the bileduct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bileduct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bileduct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bileduct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. PMID:23716999

We present the first case of an intraductal papillary neoplasm of the bileduct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bileduct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bileduct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bileduct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. PMID:23716999

Intraductal papillary mucinous neoplasm (IPMN) of the bileduct is still rare and not yet understood despite of its increased incidence and similar clinicopathologic characteristics compared with IPMN of the pancreas. The fistula formation into other organs can occur in IPMN, especially the pancreatic type. To our knowledge, only two cases of IPMN of the bileduct with a choledochoduodenal fistula were reported and we have recently experienced a case of IPMN of the bileduct penetrating into two neighboring organs of the stomach and duodenum presenting with abdominal pain and jaundice. Endoscopy showed thick mucin extruding from two openings of the fistulas. Endoscopic suction of thick mucin using direct peroral cholangioscopy with ultra-slim endoscope through choledochoduodenal fistula was very difficult and ineffective because of very thick mucin and next endoscopic suction through the stent after prior insertion of biliary metal stent into choledochogastric fistula also failed. Pathologic specimen obtained from the proximal portion of the choledochogastric fistula near left intrahepatic bileduct through the metal stent showed a low grade adenoma. The patient declined the surgical treatment due to her old age and her abdominal pain with jaundice was improved after percutaneous transhepatic biliary drainage with the irrigation of N-acetylcysteine three times daily for 10 d. PMID:25031793

A patient with intermittent right upper quadrant abdominal pain thought to represent acute cholecystitis had common bileduct obstruction due to an enlarged right renal pelvis. A Tc-99m-HIDA scan provided the first clue to the diagnosis. The case reinforces the value of cholescintigraphy in diagnosing pathology outside the biliary system.

Vitamin K1 is used as a liver protection drug for cholestasis-induced liver fibrosis in China, but the mechanism of vitamin K1's action in liver fibrosis is unclear. In this study, a model of liver fibrosis was achieved via bileduct ligation in rats. The rats were then injected with vitamin K1, and the levels of serum aspartate aminotransferase, alanine transaminase, total bilirubin and the fibrotic grade score, collagen content, the expressions of α-smooth muscle actin (SMA) and cytokeratin 19 (CK19) were measured on day 28 after ligation. The levels of the biochemical parameters, fibrotic score and collagen content were significantly reduced by treatment with vitamin K1 in bileduct-ligated rats. In addition, α-SMA and CK19 expression was significantly reduced by vitamin K1 treatment in bileduct-ligated rats. These results suggested that vitamin K1 may attenuate liver fibrosis by inhibiting hepatic stellate cell activation in bileduct-ligated rats. PMID:24742111

In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well as to excrete bilirubin and other metabolic products. In the liver, the experimental obstruction of the extrahepatic biliary system initiates a complex cascade of pathological events that leads to cholestasis and inflammation resulting in a strong fibrotic reaction originating from the periportal fields. Therefore, surgical ligation of the common bileduct has become the most commonly used model to induce obstructive cholestatic injury in rodents and to study the molecular and cellular events that underlie these pathophysiological mechanisms induced by inappropriate bile flow. In recent years, different surgical techniques have been described that either allow reconnection or reanastomosis after bileduct ligation (BDL), e.g., partial BDL, or other microsurgical methods for specific research questions. However, the most frequently used model is the complete obstruction of the common bileduct that induces a strong fibrotic response after 21 to 28 days. The mortality rate can be high due to infectious complications or technical inaccuracies. Here we provide a detailed surgical procedure for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959. PMID:25741630

Background: Ultrasonography is the diagnostic method of choice for visualization and rational work-up of abdominal organs. The dilatation of the common bileduct helps distinguish obstructive from non-obstructive causes of jaundice. Availability of normal measurements of the common bileduct is therefore important. There exists significant variations in the anthropometric features of various populations, regions and races. Aim: Study was conducted to obtain data on sonographically measured diameters of common bileduct in a series of normal Rajasthani population and to measure its correlation with age, sex and anthropometry. Setting and Design: Cross-sectional hospital-based study conducted at Mahatma Gandhi Medical College and Hospital, Jaipur, India. Materials and Methods: Study included 200 participants with equal proportion belonging to either sex. Common bileduct was measured at three locations- at the porta hepatis, in the most distal aspect of head of pancreas and mid-way between these points. Anthropometric measurements including height, weight, chest circumference, circumference at transpyloric plane, circumference at umbilicus and circumference at hip were obtained using standard procedures. Statistical Analysis: Univariable analysis with measures of frequency and standard deviation and bivariable analysis using correlation. Results: Mean age of study subjects was 34.5 years (Range 18-85 years). Mean diameters of the common bileduct in the three locations were: proximal, 4.0 mm (SD 1.02 mm); middle, 4.1 mm (SD 1.01 mm); and distal, 4.2 mm (SD 1.01 mm) and overall mean for all measures 4.1 mm (SD 1.01 mm). Average diameter ranged from 2.0 mm to 7.9 mm, with 95 percent of the subjects having a diameter of less than 6 mm. We observed a statistically significant relation of common bileduct with age, along with a linear trend. There was no statistically significant difference in common bileduct diameter between male and female subjects. The diameter did

OBJECTIVES: There is little data on the natural history of asymptomatic bileduct stones and hence there is uncertainty on the management of asymptomatic bileduct stones discovered incidentally at the time of laparoscopic cholecystectomy. We retrospectively reviewed a group of patients who had previously underwent laparoscopic cholecystectomy, but who did not have a pre-operative suspicion of intra-ductal stones, to determine if any biliary complications had subsequently developed. A group of patients who had no pre-operative suspicion of intra-ductal stones, but routinely underwent intraoperative cholangiogram (IOC) at time of cholecystectomy, served as the control group. METHODS: A telephone questionnaire was completed by each patient's family practitioner in 59 of 79 (75%) patients who underwent laparoscopic cholecystectomy. In the remaining 20 patients additional information was obtained from hospital records and from the central services agency (CSA). These patients had no pre-operative suspicion of bileduct stones and therefore did not undergo an IOC or ERCP. The control group (73 patients) had no pre-operative suspicion of bileduct stones but had a routine IOC performed to define the biliary anatomy. RESULTS: 59 patients were followed up for an average of 57 months (range 30-78 months) after laparoscopic cholecystectomy. None of these patients developed pancreatitis, jaundice, deranged liver function tests (LFT's), or required ERCP or other biliary intervention. In the additional 20 patients where no information was available from the family practitioner, 11 patients had follow up appointments with no documentation of biliary complications or abnormal LFT's. 19 of 20 patients were traceable through the CSA and were all alive. Only 1 patient was untraceable and therefore unknown if biliary complications had developed. In the control group, 4 of 73 (6%) patients had intraductal stones detected and extracted. Thus the prevalence of asymptomatic bileduct

Objectives: Clinical evidence regarding radiological–endoscopic management of intrahepatic bileduct stones is currently lacking. Our aim is to report our 18-year experience in combined radiological–endoscopic management of intrahepatic difficult bileduct stones. Methods: From June 1994 to June 2012, 299 symptomatic patients with difficult bileduct stones were admitted to our institution. Percutaneous transhepatic cholangiography (PTC)/biliary drainage/s was performed, dilating the PTC track to 10 or 16 French within 3–7 days. Afterward we carried out percutaneous transhepatic cholangioscopy (PTCS) with electrohydraulic lithotripsy (EHL) and/or interventional radiology techniques. Follow up was made with clinical/laboratory tests and ultrasound (US). We retrospectively analyzed our radiological–endoscopic approach and reported our technical and clinical outcomes. Results: Complete stone clearance was achieved in 298 patients after a maximum of 4 consecutive sessions. Most patients (64.6%) were treated with PTCS/EHL alone, while the remaining with radiological techniques alone (26%) or a combination of both techniques (13.3%). Recurrence of stones occurred in 45 cases (15%, Tsunoda class III and class IV) within 2 years and were successfully retreated. Major adverse events were: 5 (1.6%) cases of massive bleeding that required embolisation, 2 (0.66%) perforations of the common bileduct and 31 cases (10.3%) of acute cholangitis managed with medical therapy or intervention. Conclusion: After 18 years of experience we demonstrated that our combined radiological–endoscopic approach to ‘difficult bileduct stones‘ may result in both immediate and long-term clearance of stones with a low rate of adverse events. PMID:26557890

In patients with hepatocellular carcinoma (HCC), the presence of bileduct tumor thrombi (BDTT) in the major bileducts indicates poor prognosis compared with that of HCC patients without BDTT. However, the prognostic significance of incidental microscopic BDTT in the peripheral bileducts after curative liver resection is not known. We compared the outcomes of HCC patients with and without microscopic BDTT in the peripheral bileducts who underwent hepatectomy.The electronic medical records of 31 patients with microscopic BDTT (BDTT group) were retrospectively reviewed. To compare the surgical outcomes, 62 patients (No BDTT group) were randomly chosen from the remaining HCC patients without BDTT based on age, sex, etiology of HCC, tumor size, tumor number, and modified Union for International Cancer Control T staging.The 1-year, 2-year, and 3-year disease-free survival rates and overall survival rates were 54.8%, 34.0%, 34.0% and 90.1%, 69.2%, 61.0% in the BDTT group and 66.8%, 59.2%, 42.3% and 86.4%, 84.4%, 84.4% in the No BDTT group (P = 0.089 and P = 0.014, respectively). The overall survival curve in the No BDTT group was higher than that in the BDTT group. Multivariate analysis revealed that predisposing factors for tumor recurrence after curative liver resection included increased levels of the protein induced by vitamin K antagonist-II (PIVKA-II), tumor grades 3 and 4, and the presence of BDTT.This study demonstrates that HCC prognosis is worse in patients with incidental microscopic BDTT in the peripheral bileducts than it is in those without BDTT. The presence of BDTT should therefore be considered when evaluating a patient's HCC prognosis after curative hepatectomy. PMID:25674733

Abstract In patients with hepatocellular carcinoma (HCC), the presence of bileduct tumor thrombi (BDTT) in the major bileducts indicates poor prognosis compared with that of HCC patients without BDTT. However, the prognostic significance of incidental microscopic BDTT in the peripheral bileducts after curative liver resection is not known. We compared the outcomes of HCC patients with and without microscopic BDTT in the peripheral bileducts who underwent hepatectomy. The electronic medical records of 31 patients with microscopic BDTT (BDTT group) were retrospectively reviewed. To compare the surgical outcomes, 62 patients (No BDTT group) were randomly chosen from the remaining HCC patients without BDTT based on age, sex, etiology of HCC, tumor size, tumor number, and modified Union for International Cancer Control T staging. The 1-year, 2-year, and 3-year disease-free survival rates and overall survival rates were 54.8%, 34.0%, 34.0% and 90.1%, 69.2%, 61.0% in the BDTT group and 66.8%, 59.2%, 42.3% and 86.4%, 84.4%, 84.4% in the No BDTT group (P = 0.089 and P = 0.014, respectively). The overall survival curve in the No BDTT group was higher than that in the BDTT group. Multivariate analysis revealed that predisposing factors for tumor recurrence after curative liver resection included increased levels of the protein induced by vitamin K antagonist-II (PIVKA-II), tumor grades 3 and 4, and the presence of BDTT. This study demonstrates that HCC prognosis is worse in patients with incidental microscopic BDTT in the peripheral bileducts than it is in those without BDTT. The presence of BDTT should therefore be considered when evaluating a patient's HCC prognosis after curative hepatectomy. PMID:25674733

Four patients who complained of symptoms and signs compatible with biliary tract disease and in whom the diagnosis of gallbladder (three cases) and common bileduct ascariasis (one case) was made sonographically are reported. In two patients with gallbladder ascariasis, cholecystectomy corroborated the presence of the round-worms, and was curative. The third patient was a pregnant woman (32nd gestational week) who took piperazine citrate, and a second sonogram performed 29 days later was completely normal. The fourth patient with common bileduct ascariasis underwent choledochotomy with extraction of one ascaris lumbricoides from the common duct, and a T tube was left in place for 15 days. All patients received antiparasitics and had a favorable outcome. Ultrasonography is an important noninvasive diagnostic procedure in the work-up of these patients, who usually describe a clinical picture suggesting gallstone disease: this is especially true in the presence of pregnancy. PMID:8351609

Since the first silk suture material acting as a nidus for the development of subsequent common bileduct stones after cholecystectomy was described in 1897, several investigators have reported that suture materials may cause choledocholithiasis. Silk, chromic catgut, parasites, and other foreign bodies are known occasionally to form such niduses in the common bileduct. Surgical hemostatic clips have been used widely and generally are considered very safe. The first case of postcholecystectomy clip migration was reported in 1979. Its exact pathogenesis remains unknown; it generally is agreed that bileduct injuries, inappropriate clip placements, subclinical bile leak, and infections also have been postulated to contribute to clip migration. We report an unusual case in which the core of a biliary calculus in the common bileduct was found to contain a surgical clip. This case illustrates the potentially abrupt and late development of clip-related gallstones and highlights the need for long-term follow-up evaluation. PMID:21943951

OBJECTIVE: To establish a simple, reproducible, and safe technique of laparoscopic common bileduct exploration (CBDE) with high clearance rates and low morbidity and mortality rates. SUMMARY BACKGROUND DATA: For most general surgeons, laparoscopic CBDE appears an unduly complex and demanding procedure. Since the introduction of laparoscopic cholecystectomy, many surgeons use endoscopic cholangiography (ERC) and endoscopic sphincterotomy as their only option in treating bileduct stones. ERC is more specific if used after surgery, but it carries an appreciable morbidity rate and has the disadvantage of requiring a second procedure to deal with bileduct stones. To this end, various methods of laparoscopic CBDE have been developed. METHODS: Between August 1991 and February 1997, 300 consecutive unselected patients underwent laparoscopic CBDE. RESULTS: Of 300 laparoscopic CBDE procedures, 173 (58%) were managed using a transcystic approach and 127 (42%) with choledochotomy. Successful laparoscopic stone clearance was achieved in 271 (90%). Of the 29 (10%) patients not cleared laparoscopically, 10 had an elective postsurgical ERC, 12 were converted to an open procedure early in the series, and 7 had unexpected retained stones. There was one death (mortality rate 0.3%) and major morbidity occurred in 22 patients (7%). The last 100 procedures were performed from July 1995 to February 1997, and stone clearance was unsuccessful in only two patients. CONCLUSIONS: Laparoscopic transcystic basket extraction of common duct stones under fluoroscopic guidance is a relatively quick, successful, and safe technique. Choledochotomy, when required, is associated with a higher morbidity rate, particularly with T-tube insertion, and the authors advocate primary bileduct closure with or without insertion of a biliary stent as a more satisfactory technique for both surgeon and patient. Most patients with gallbladder and common duct calculi should expect a curative one

Background/Aims The efforts to improve biliary plastic stents (PSs) for decreasing biofilm formation and overcome short patency time have been continued. The aim of this study is to evaluate the effect of advanced hydrophilic coating for patency and biodurability of PS. Methods Using an in vitro bile flow phantom model, we compared patency between prototype PS with hydrophilic coating (PS+HC) and prototype PS without hydrophilic coating (PS−HC). We performed an analysis of the degree of luminal narrowing by microscopic examination. Using an in vivo swine bileduct dilation model made by endoscopic papillary closure and stent insertion, we evaluated biodurability of hydrophilic coating. Results In the phantom model, PS+HC showed less biofilm formation and luminal narrowing than PS−HC at 8 weeks (p<0.05). A total of 31 stents were inserted into the dilated bileduct of seven swine models, and 24 stents were successfully retrieved 8 weeks later. There was no statistical difference of stent patency between the polyethylene PS+HC and the polyurethane PS+HC. The biodurability of hydrophilic coating was sustained up to 8 weeks, when assessing the coating layer by scanning electron microscopy examination. Conclusions Advanced hydrophilic coating technology may extend the patency of PS compared to uncoated PS. PMID:27021507

In this case report, we describe the extremely rare case of a collision tumor comprising cancers of the bileduct and the pancreas. A 70-year-old man was referred to our hospital with a diagnosis of obstructive jaundice. He was diagnosed with pancreatic head cancer, and we performed a pancreaticoduodenectomy with lymph node dissection. At laparotomy, there were two palpable masses in the vicinity of the confluence of the cystic duct and the head of the pancreas. The resected specimen demonstrated tumors at the confluence of the cystic duct and in the pancreatic head. Histopathological examination demonstrated a moderately differentiated tubular adenocarcinoma in the pancreatic head and a well-differentiated tubular adenocarcinoma at the confluence of the cystic duct. Immunostaining was negative for p53 and MUC6 in the pancreatic head tumor; however, immunostaining was positive for both in the tumor located at the confluence of the cystic duct. The two tumors were histologically different and were diagnosed as collision cancer caused by the collision of the bileduct and pancreatic cancers. PMID:26943405

Background BileDuct Injuries (BDI) during cholecystectomy are now being recognized as major health problems. Objectives Herein, we present our experience with handling major BDIs and report long-term outcome of hepaticojejunostomies followed by trans-jejunal hepatic duct stenting performed to reconstruct extra-hepatic biliary tracts. Materials and Methods In this case series, we prospectively collected data of 22 patients, who underwent first time biliary reconstruction through Roux-en-y hepaticojejunostomy followed by hepatic duct stenting using a trans-jejunal bifurcated 6F tube drain. The long-term outcome was assessed and defined as excellent (asymptomatic, normal liver enzymes and bilirubin levels), good (asymptomatic, mild abnormality in liver enzyme and bilirubin levels), poor (symptomatic, abnormal liver enzymes and bilirubin level) and failure (requiring reoperation). Results A total of 22 patients including four males (18.1%) and 18 females (81.8%) were evaluated. The mean age was 42.71 (range: 23 - 74) years. Twelve patients had undergone open cholecystectomy (54.5%) and the rest had a history of laparoscopic cholecystectomy. The mean interval between the primary operation and reconstruction was 92.71 days. The mean follow-up period after biliary reconstruction was 42.33 (range: 1 - 96) months. No instance of anastomotic leakage or stenosis, biliary sepsis, thromboembolic event, or respiratory infection was noted in the long-term follow-up. The outcome was excellent in all patients. No case with poor or failure of result was noticed. Conclusions Although a devastating complication iatrogenic major bileduct injuries can be corrected surgically with a high rate of success. Temporary trans-jejunal stenting of the hepatic ducts can help in maintaining the integrity of anastomosis without stenosis or biliary sepsis. PMID:27626003

Purpose: To determine the effectiveness of percutaneous transhepatic removal of bileduct stones when the procedure of endoscopic therapy fails for reasons of anatomical anomalies or is rejected by the patient. Methods: Between April 2001 and May 2010, 261 patients (138 male patients and 123 female patients; age range, 14-92 years; mean age, 64.6 years) with bileduct stones (common bileduct [CBD] stones = 248 patients and hepatolithiasis = 13 patients) were included in the study. Percutaneous transhepatic cholangiography was performed, and stones were identified. Percutaneous transhepatic balloon dilation of the papilla of Vater was performed. Then stones were pushed out into the duodenum with a Fogarty balloon catheter. If the stone diameter was larger than 15 mm, then basket lithotripsy was performed before balloon dilation. Results: Overall success rate was 95.7%. The procedure was successful in 97.5% of patients with CBD stones and in 61.5% of patients with hepatolithiasis. A total of 18 major complications (6.8%), including cholangitis (n = 7), subcapsular biloma (n = 4), subcapsular hematoma (n = 1), subcapsular abscess (n = 1), bile peritonitis (n = 1), duodenal perforation (n = 1), CBD perforation (n = 1), gastroduodenal artery pseudoaneurysm (n = 1), and right hepatic artery transection (n = 1), were observed after the procedure. There was no mortality. Conclusion: Our experience suggests that percutaneous transhepatic stone expulsion into the duodenum through the papilla is an effective and safe approach in the nonoperative management of the bileduct stones. It is a feasible alternative to surgery when endoscopic extraction fails or is rejected by the patient.

Purpose: To determine the effectiveness of percutaneous transhepatic removal of bileduct stones when the procedure of endoscopic therapy fails for reasons of anatomical anomalies or is rejected by the patient. Methods: Between April 2001 and May 2010, 261 patients (138 male patients and 123 female patients; age range, 14-92 years; mean age, 64.6 years) with bileduct stones (common bileduct [CBD] stones = 248 patients and hepatolithiasis = 13 patients) were included in the study. First, percutaneous transhepatic cholangiography was performed and stones were identified. Percutaneous transhepatic balloon dilation of the papilla of Vater was performed. Then stones were pushed out into the duodenum with a Fogarty balloon catheter. If the stone diameter was larger than 15 mm, then basket lithotripsy was performed before balloon dilation. Results: Overall success rate was 95.7%. The procedure was successful in 97.5% of patients with CBD stones and in 61.5% of patients with hepatolithiasis. A total of 18 (6.8%) major complications, including cholangitis (n = 7), subcapsular biloma (n = 4), subcapsular hematoma (n = 1), subcapsular abscess (n = 1), bile peritonitis (n = 1), duodenal perforation (n = 1), CBD perforation (n = 1), gastroduodenal artery pseudoaneurysm (n = 1), and right hepatic artery transection (n = 1), were seen after the procedure. There was no mortality. Conclusion: Our experience suggests that percutaneous transhepatic stone expulsion into the duodenum through the papilla is an effective and safe approach in the nonoperative management of the bileduct stones. It is a feasible alternative to surgery when endoscopic extraction fails or is rejected by the patient.

Abstract Biliary strictures and bile leaks account for the majority of biliary complications after living donor liver transplantation (LDLT). The aim of this study was to examine differences in biliary complications after adult LDLTs were performed by an experienced senior surgeon and an inexperienced junior surgeon. Surgeries included bileduct reconstruction after adult LDLT using a right liver graft, and risk factors for biliary stricture were identified. We retrospectively reviewed the medical records of 136 patients who underwent LDLT in order to identify patients who developed biliary complications. The senior surgeon performed 102 surgeries and the junior surgeon performed 34 surgeries. The proportion of patients with biliary stricture was similar between the senior and the junior surgeons (27.5% vs 26.5%; P = 0.911). However, the incidence of biliary leakage was higher in patients of the junior surgeon than in those of the senior surgeon (23.5% vs 2.9%; P = 0.001). The frequency of percutaneous drainage was also higher for the junior surgeon than the senior surgeon because of the junior surgeon’s high leakage rate of the drainage. When the junior surgeon performed bileduct anastomosis, biliary leakage occurred in 7 patients between the 11th and 20th cases. However, biliary leakage occurred in only 1 case thereafter. Bileduct reconstruction performed by beginner surgeons in LDLT using right lobe grafts should be cautiously monitored and observed by a senior surgeon until an inexperienced junior surgeon has performed at least 20 cases, because of the high incidence of biliary leakage related to surgeon’s inexperience in bileduct reconstructions in LDLT. PMID:25255023

Acquired immune deficiency syndrome increases the risk of developing non-Hodgkin's B-cell lymphoma (NHL) (relative risk over 100). NHL tend to be high-grade and to affect the central nervous system and digestive tract. Biliary tract compression is usually due to external compression from enlarged lymph nodes, but is not usually the first manifestation.We describe 2 cases of bileduct obstruction secondary to NHL in patients diagnosed with HIV infection. Histological diagnosis of the lymphoma can be difficult but is necessary so that these patients do not undergo highly aggressive surgical treatment instead of chemotherapy, which currently produces the best results. Therefore, we emphasize the importance of including lymphomas in the differential diagnosis of bileduct obstruction in patients with HIV infection. PMID:14670238

Biliary atresia (BA) is an infantile obstructive cholangiopathy of unknown etiology with suboptimal therapy, which is responsible for 40 to 50% of all pediatric liver transplants. Although the etiology of bileduct injury in BA in unknown, it is postulated that a pre- or perinatal viral infection initiates cholangiocyte apoptosis and release of antigens that trigger a Th1 immune response that leads to further bileduct injury, inflammation, and obstructive fibrosis. Humoral immunity and activation of the innate immune system may also play key roles in this process. Moreover, recent investigations from the murine BA model and human data suggest that regulatory T cells and genetic susceptibility factors may orchestrate autoimmune mechanisms. What controls the coordination of these events, why the disease only occurs in the first few months of life, and why a minority of infants with perinatal viral infections develop BA are remaining questions to be answered. PMID:23397531

Thirty patients with cystic disease of the bileducts operated on between 1965 and 1985 were reviewed. Three patients (10%) had a synchronous adenocarcinoma, and in three patients (10%) a metachronous carcinoma developed for a total incidence of malignancy of 20%. All patients died within 1 year of the diagnosis of malignancy. Of 19 benign cysts available for pathologic examination, one third had proliferative epithelial changes, and in two of these patients a metachronous carcinoma developed. Goblet cell metaplasia was prominent in four patients. This suggests the possibility that dysplastic changes and metaplasia of the epithelium could give rise to carcinoma. Resection of benign cysts of the bileducts is favored, when feasible, in an attempt to decrease the incidence of malignancy. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:3566373

Biliary laser lithotripsy was performed under direct visual control in 35 consecutive patients not amenable to routine endoscopy. The patients had 1-50 (median 1) bileduct stones with the greatest diameter of the largest stone being 9-42 mm (median 20 mm). Conventional endoscopic treatment had failed because of an inaccessible papilla (16 patients), biliary strictures (seven patients), and impaction or large size of calculi (12 patients). Twelve patients, depending on their anatomical condition, underwent peroral cholangioscopy by means of a mother-babyscope system. Percutaneous cholangioscopy was initially carried out in 23 patients, 7-20 days (median 10 days) after creation of a transhepatic fistula. Pulsed dye laser (32 patients) or alexandrite laser (three patients) lithotripsy was applied under an appropriate direct visual control in all cases. Complete stone disintegration succeeded in 33 of 35 patients. All resultant fragments passed the papilla within a mean number of 1.3 treatment sessions. Peroral cholangioscopic lithotripsy failed in two cases. One patient successfully underwent percutaneous laser treatment and the other patient was referred to surgery. Fever, temporary haemobilia, or a subcapsular liver haematoma were seen in a total of eight patients during establishment of the cutaneobiliary fistula. A 95 year old patient who had been admitted with septic cholangitis died because of cardiorespiratory failure 5 days after bileduct clearance. It is concluded that laser lithotripsy performed under a direct visual control is an effective and safe procedure for the non-surgical treatment of difficult bileduct stones. Ductal clearance can usually be achieved in a single treatment session when the papilla and the stones are accessible by the peroral route. Percutaneous cholangioscopic lithotripsy is more time consuming but highly effective even in patients with a difficult anatomy, bileduct strictures, or intrahepatic calculi. This approach should be

Bileduct cancers are increasing in frequency while being difficult to diagnose. Currently available endoscopic imaging devices used in the biliary tree are low resolution with poor image quality, leading to inadequate evaluation of indeterminate biliary strictures. However, a new ultrathin and flexible cholangioscope system has been successfully demonstrated in a human subject. This mini-cholangioscope system uses a scanning fiber endoscope (SFE) as a forward-imaging guidewire, dimensions of 1.2-mm diameter and 3-m length. Full color video (500-line resolution at 30Hz) is the standard SFE imaging mode using spiral scanning of red, green, and blue laser light at low power. Image-guided operation of the biopsy forceps was demonstrated in healthy human bileducts with and without saline flushing. The laser-based video imaging can be switched to various modes to enhance tissue markers of disease, such as widefield fluorescence and enhanced spectral imaging. In parallel work, biochemical discrimination of tissue health in pig bileduct has been accomplished using fiberoptic delivery of pulsed UV illumination and time-resolved autofluorescence spectroscopic measurements. Implementation of time-resolved fluorescence spectroscopy for biochemical assessment of the bileduct wall is being done through a secondary endoscopic channel. Preliminary results indicate that adequate SNR levels (> 30 dB) can be achieved through a 50 micron fiber, which could serve as an optical biopsy probe. The SFE is an ideal mini-cholangioscope for integration of both tissue and molecular specific image contrast in the future. This will provide the physician with unprecedented abilities to target biopsy locations and perform endoscopically-guided therapies.

β-catenin and c-myc play important roles in the development of tissues and organs. However, little is known about their expression patterns during the development of the human common bileduct. Immunohistochemistry was used to detect β-catenin and c-myc expression in common bileduct samples from postmortem tissues of 14 premature infants and 6 spontaneously aborted fetuses. The expression of β-catenin and c-myc was also analyzed by Western blot. The samples were divided into four groups based on the stage of human fetal development: 12, 13-27, 28-37, and >37 weeks. The Image-Pro Plus v. 6.0 image analysis software was used to calculate the mean qualifying score (MQS). At fetal stages 12, 13-27, 28-37, and >37 weeks, MQS of β-catenin were 612.52±262.13, 818.38±311.73, 706.33±157.19, and 350.69±110.19, respectively. There was a significant difference in MQS among the four groups (ANOVA, P=0.0155) and between the scores at >37 and 13-27 weeks (Student-Newman-Keuls, P<0.05). At fetal stages 12, 13-27, 28-37, and >37 weeks, the MQS of c-myc were 1376.64±330.04, 1224.18±171.66, 1270.24±320.75, and 741.04±219.19, respectively. There was a significant difference in MQS among the four groups (ANOVA, P=0.0087) and between the scores at >37 and 12 weeks, >37 and 13-27 weeks, and >37 and 28-37 weeks (all P<0.05, Student-Newman-Keuls). Western blots showed that β-catenin and c-myc expression were significantly higher in fetal than in postnatal control duct tissue (P<0.05). c-myc and β-catenin are involved in the normal development of the human common bileduct. PMID:25003633

In the last decades many advances have been achieved in endoscopy, in the diagnosis and therapy of cholangiocarcinoma, however blood test, magnetic resonance imaging, computed tomography scan may fail to detect neoplastic disease at early stage, thus the diagnosis of cholangiocarcinoma is achieved usually at unresectable stage. In the last decades the role of endoscopy has moved from a diagnostic role to an invaluable therapeutic tool for patients affected by malignant bileduct obstruction. One of the major issues for cholangiocarcinoma is bileducts occlusion, leading to jaundice, cholangitis and hepatic failure. Currently, endoscopy has a key role in the work up of cholangiocarcinoma, both in patients amenable to surgical intervention as well as in those unfit for surgery or not amenable to immediate surgical curative resection owing to locally advanced or advanced disease, with palliative intention. Endoscopy allows successful biliary drainage and stenting in more than 90% of patients with malignant bileduct obstruction, and allows rapid reduction of jaundice decreasing the risk of biliary sepsis. When biliary drainage and stenting cannot be achieved with endoscopy alone, endoscopic ultrasound-guided biliary drainage represents an effective alternative method affording successful biliary drainage in more than 80% of cases. The purpose of this review is to focus on the currently available endoscopic management options in patients with cholangiocarcinoma. PMID:26078827

Surgical fraternity has not yet arrived at any consensus for adequate treatment of choledocholithiasis. Sequential treatment in the form of pre-operative endoscopic retrograde cholangio-pancreatography followed by laparoscopic cholecystectomy (LC) is considered as optimal treatment till date. With refinements in technique and expertise in field of minimal access surgery, many centres in the world have started offering one stage management of choledocholithiasis by LC with laparoscopic common bileduct exploration (LCBDE). Various modalities have been tried for entering into concurrent common bileduct (CBD) [transcystic (TC) vs transcholedochal (TD)], for confirming stone clearance (intraoperative cholangiogram vs choledochoscopy), and for closure of choledochotomy (T-tube vs biliary stent vs primary closure) during LCBDE. Both TC and TD approaches are safe and effective. TD stone extraction is involved with an increased risk of bile leaks and requires more expertise in intra-corporeal suturing and choledochoscopy. Choice depends on number of stones, size of stone, diameter of cystic duct and CBD. This review article was undertaken to evaluate the role of LCBDE for the management of choledocholithiasis. PMID:27231516

Recent studies have suggested that a peculiar tumor mimicking intraductal tubulopapillary neoplasms (ITPN) of the pancreas can develop in the bileduct. Here, we present a similar case and review the published work on the newly proposed biliary neoplasm. A 68-year-old woman was referred to us for further evaluation of a liver mass. On imaging, the tumor was 40 mm in size and intraductal in location, and was enhanced slightly on the contrast-enhanced computed tomography. No mucin overproduction was found. She underwent right hepatectomy for suspected intraductal papillary neoplasm of the bileduct. The tumor histologically consisted of the biliary-type epithelium arranged in a tubular architecture within the dilated bileduct. Tumor cells had features of high-grade dysplasia but no stroma invasion. No expressions of MUC2 and MUC5AC were noted. On molecular studies, KRAS and GNAS appeared to be wild-type genotypes. These features were in keeping with ITPN. In the published work review, "biliary ITPN" described in four manuscripts were characterized by predominantly intrahepatic/hilar in location, histological tubular architecture, negative expressions of MUC2 and MUC5AC, and uncommon alterations of KRAS, GNAS and BRAF. Although invasive malignancy was present in 71%, the outcome was favorable with the 5-year survival expected to be approximately 90%. Biliary ITPN are supposedly uncommon, but a greater awareness of this condition may give more chance to diagnose the underrecognized neoplasm. PMID:26459784

Surgical fraternity has not yet arrived at any consensus for adequate treatment of choledocholithiasis. Sequential treatment in the form of pre-operative endoscopic retrograde cholangio-pancreatography followed by laparoscopic cholecystectomy (LC) is considered as optimal treatment till date. With refinements in technique and expertise in field of minimal access surgery, many centres in the world have started offering one stage management of choledocholithiasis by LC with laparoscopic common bileduct exploration (LCBDE). Various modalities have been tried for entering into concurrent common bileduct (CBD) [transcystic (TC) vs transcholedochal (TD)], for confirming stone clearance (intraoperative cholangiogram vs choledochoscopy), and for closure of choledochotomy (T-tube vs biliary stent vs primary closure) during LCBDE. Both TC and TD approaches are safe and effective. TD stone extraction is involved with an increased risk of bile leaks and requires more expertise in intra-corporeal suturing and choledochoscopy. Choice depends on number of stones, size of stone, diameter of cystic duct and CBD. This review article was undertaken to evaluate the role of LCBDE for the management of choledocholithiasis. PMID:27231516

There are a variety of procedures to use once a common bileduct stone is discovered at the time of cholecystectomy. To be cost-effective, the surgeon must know how much money will be spent with each procedure chosen. Cost data is largely unavailable because costs are difficult to estimate and charge data are jealously guarded. In addition, costs are not the same at different hospitals and therefore cannot be compared. The factors that increase costs for treating bileduct stones are outlined in this report and real costs are used from one hospital to help with illustration. Surgical costs vary with the severity of the disease, the amount of operating room time required, and length of stay. These surgical costs can be avoided by choosing endoscopic retrograde cholangiopancreatography, but the new costs increase almost twice that of a successful laparoscopic common bileduct exploration. Knowledge of the pattern of choledocholithiasis, the varieties of treatment, the cost implications, and the outcomes of each are the subject of this report. PMID:11323767

Purpose: To report our experience in the use of percutaneous extraction of common bileduct stones detected in the post-cholecystectomy period. Methods: Forty-two patients in whom endoscopic cannulation and/or sphincterotomy had failed or could not be done due to several reasons underwent balloon dilatation of the ampulla of Vater and subsequent advancement of the stones via the percutaneous transhepatic route or T-tube tract. Results: The procedure was successful in 42 cases. In three patients, stones were crushed in the common bileduct and pushed as fragments into the duodenum. In all cases transient adverse effects were observed. There were no major complications. All cases were checked with ultrasonography for 6 months after the procedure. Conclusion: Percutaneous extraction of common bileduct stones is an effective method of treatment with a high success rate,low complication rate and shorter hospital stay. It may serve as an alternative method in cases where endoscopic removal of stones fails.

Lead is very common in the environment, and it is therefore important to characterize its possible adverse health effects. The aim of this study was to evaluate the impact of lead exposure on selected functions of the liver and bileducts in people who are chronically exposed to the metal because of their occupations. To provide this information, the activity of specific enzymes and the bilirubin concentration were determined in blood serum, and morphological parameters of the liver and bileducts were evaluated using the ultrasonic imaging method. Healthy male employees of a lead-zinc processing facility (n = 145) who were occupationally exposed to lead were divided into two subgroups as a function of the lead concentrations in blood (PbB): low lead exposure (PbB = 20-35 μg/dl; n = 57) and high lead exposure (PbB = 35-60 μg/dl; n = 88). Human exposure to lead compounds was found to cause liver enlargement and to activate inflammatory reactions with the characteristics of moderate cholestasis within the bileducts, while no characteristics of necrotic damage of hepatic cells were noted. It seems that lipid peroxidation can be one of the toxic mechanisms of lead which induce moderate cholestasis. The effects depend on the extent of the lead exposure and were greater in subjects with higher exposure levels, particularly subjects with PbB values greater than 35 μg/dl. PMID:23529799

An 83-year-old woman, diagnosed as having cholelithiasis, was admitted to the Department of Surgery, Nippon Medical School, with right hypochondrial pain. Ultrasonography and computed tomography revealed a mass in the gallbladder fundus and a hypovascular tumor in the anterior segment of the liver. Magnetic resonance imaging showed stenosis of the intrahepatic bileduct and dilatation of its proximal portion. She was diagnosed as having intrahepatic bileduct carcinoma combined with gallbladder carcinoma. At laparotomy, there was evidence of multiple peritoneal metastases and intraoperative histological examination of the gallbladder tumor revealed adenocarcinoma. Accordingly, only cholecystectomy and needle biopsy of the liver tumor was performed. Histological examination of the gallbladder revealed papillary adenocarcinoma invading the muscularis propria with medullary growth or intermediate stroma. There was no microvessel invasion, no perineural invasion and no lymph node involvement. On the other hand, the liver tumor was a cholangiocarcinoma with a well-differentiated tubular pattern. Therefore, this was a rare case of synchronous carcinoma of the gallbladder associated with intrahepatic bileduct carcinoma. PMID:10690592

This study describes the value of endoscopic retrograde cholangiopancreatography (ERCP) in patients with bileduct injury after laparoscopic cholecystectomy. Twelve consecutive patients were studied over a one year period. In all patients the biliary tree was visualised during ERCP. Four patients had complete bileduct obstruction, seven patients had a stricture (two with concomitant leakage), and one patient had leakage from a hepatic branch. Three patients with complete obstruction, presented with a relatively prolonged symptom free, 'silent' period before diagnosis. In all four patients with complete transection, a proximal hepaticojejunostomy was performed. In one patient with a tough fibrous stricture, secondary to incorrect clip placement, passage of the guidewire was impossible, leaving surgical reconstruction as the only therapeutic option. All remaining seven patients with leakage or strictures, or both were successfully treated by endoscopic sphincterotomy only (n = 1) or sphincterotomy and subsequent stent placement (n = 6). When patients do not recover uneventfully after laparoscopic cholecystectomy even without cholestasis or jaundice, early ERCP is recommended as a safe and valuable method to detect bileduct injury and to suggest treatment. Subsequently, more than half of such patients can be treated endoscopically. Extended follow up is needed to evaluate the longterm results. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8406163

Understanding how hepatic precursor cells can generate differentiated bileducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bileduct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bileduct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bileducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3α and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, β1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bileduct formation, during which determination of MO plays a crucial role. PMID:20305811

Background Iatrogenic bileduct injuries are serious complications with patient morbidity. We hypothesized that the invisible near-infrared (NIR) fluorescence properties of methylene blue (MB) and indocyanine green (ICG) could be exploited for real-time, intraoperative imaging of the extrahepatic bileducts during open and laparoscopic surgeries. Methods 2.0 mg/kg of MB and 0.05 mg/kg of ICG were intravenously injected into 35-kg female Yorkshire pigs and the extrahepatic bileducts imaged over time using either the FLARE™ image-guided surgery system (open surgery) or a custom NIR fluorescence laparoscopy system. Surgical anatomy was confirmed using x-ray cholangiography. Contrast-to-background ratio (CBR), contrast-to-liver ratio (CLR), and chemical concentrations in the cystic duct (CD) and common bileduct (CBD) were measured, and the performance of each agent quantified. Results Using NIR fluorescence of MB, the CD and CBD could be identified with good sensitivity (CBR and CLR ≥ 4), during both open and laparoscopic surgeries, from 10 to 120 min post-injection. Functional impairment of the ducts, including constriction and injury were immediately identifiable. Using NIR fluorescence of ICG, extrahepatic bileducts did not become visible until 90 min post-injection due to strong residual liver retention, however, between 90 to 240 min, ICG provided exquisitely high sensitivity for both CD and CBD, with CBR ≥ 8 and CLR ≥ 4. Conclusions We demonstrate that two clinically available NIR fluorophores, MB fluorescing at 700 nm and ICG fluorescing at 800 nm, provide sensitive, prolonged identification of the extrahepatic bileducts and assessment of their functional status. PMID:20117813

Summary Background Preoperative knowledge of intrahepatic bileduct (IHD) anatomy is critical for planning liver resections, liver transplantations and complex biliary reconstructive surgery. The purpose of our study was to demonstrate the imaging features of various anatomical variants of IHD using magnetic resonance cholangio-pancreatography (MRCP) and their prevalence in our population. Material/Methods This observational clinical evaluation study included 224 patients who were referred for MRCP. MRCP was performed in a 1.5-Tesla magnet (Philips) with SSH MRCP 3DHR and SSHMRCP rad protocol. A senior radiologist assessed the biliary passage for anatomical variations. Results The branching pattern of the right hepatic duct (RHD) was typical in 55.3% of subjects. The most common variant was right posterior sectoral duct (RPSD) draining into the left hepatic duct (LHD) in 27.6% of subjects. Trifurcation pattern was noted in 9.3% of subjects. In 4% of subjects, RPSD was draining into the common hepatic duct (CHD) and in 0.8% of subjects into the cystic duct. Other variants were noted in 2.6% of subjects. In 4.9% of cases there was an accessory duct. The most common type of LHD branching pattern was a common trunk of segment 2 and 3 ducts joining the segment 4 duct in 67.8% of subjects. In 23.2% of subjects, segment 2 duct united with the common trunk of segment 3 and 4 and in 3.4% of subjects segment 2, 3, and 4 ducts united together to form LHD. Other uncommon branching patterns of LHD were seen in 4.9% of subjects. Conclusions Intrahepatic bileduct anatomy is complex with many common and uncommon variations. MRCP is a reliable non-invasive imaging method for demonstration of bileduct morphology, which is useful to plan complex surgeries and to prevent iatrogenic injuries. PMID:27298653

The bileduct-cannulated (BDC) rat is a standard animal model used in ADME experiments. The aim of this study was to investigate post-surgical alterations that are relevant to ADME investigations in BDC rats compared with sham- and non-operated animals. Water and food intake was reduced in the animals' post-surgery. This led to a lower body weight in operated animals. In BDC animals, aspartate aminotransferase (AST) levels in plasma were transiently elevated and total bile acid levels were reduced. Alpha(1)-acid glycoprotein (AGP) in plasma and the concentration of bile components in bile were elevated. Histopathology showed inflammation in the area of the cannulation between the liver and the small intestine. A microarray-based gene expression and RTq-PCR analysis identified altered expression for several genes involved in drug disposition including the down-regulation of cytochrome P450 enzymes. This led to reduced cytochrome P450 content in the liver and lower metabolic activity in microsomes from BDC and sham-operated rats compared with naïve animals. The results of the study suggest that the post-surgical inflammation leads to physiological changes relevant for drug absorption and disposition. These alterations should be accounted for in the interpretation of ADME studies in BDC animals. PMID:21521079

Adenomas involving the extrahepatic bileducts are rare benign tumours of the biliary tract. Given the asymptomatic nature of these tumours and the natural progression of biliary adenoma to carcinoma including cholangiocarcinoma, early detection is challenging. We present a case of an octogenarian woman with a remote history of gallstones who initially presented to the gastroenterology office for an incidental finding of biliary dilation, and whose subsequent imagings and biopsy suggested common bile adenoma. However, the patient was deemed a poor surgical candidate for pancreaticoduodenectomy, and unfortunately represented 5 months later with findings suggesting cholangiocarcinoma. This case provides a unique opportunity to study the natural progression of biliary adenoma to cholangiocarcinoma. PMID:24859557

Streptococcus pseudopneumoniae was described in 2004 as a new human pathogen, acknowledged in a range of clinical infections typically associated to the respiratory tract. This report demonstrates that S. pseudopneumoniae has the potential to cause invasive infection. In blood cultures from three patients, growth of an atypical Streptococcus pneumoniae (non-capsular, non-serotypeable, optochin susceptible under ambient atmosphere and bile-intermediately soluble) was recovered. All three patients had a history of a haematological disease (myelodysplastic syndrome and multiple myeloma) and an apparent origin of infection related to the liver or bileduct. All isolates were genome sequenced and subsequently identified as S. pseudopneumoniae by multi-locus sequence analysis (MLSA). Multi-locus sequence typing (MLST) based on the S. pneumoniae scheme revealed unknown sequence types and the antibiogram and resistome revealed no antibiotic resistance. PMID:27100044

Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bileduct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions. PMID:25007141

Background & Aims: Cholestasis is one of the principal manifestations of liver disease and often results from disorders involving bileduct epithelia rather than hepatocytes. A range of disorders affects biliary epithelia, and no unifying pathophysiologic event in these cells has been identified as the cause of cholestasis. Here we examined the role of the inositol 1,4,5-trisphosphate receptor (InsP3R)/Ca2+ release channel in Ca2+ signaling and ductular secretion in animal models of cholestasis and in patients with cholestatic disorders. Methods: The expression and distribution of the InsP3R and related proteins were examined in rat cholangiocytes before and after bileduct ligation or treatment with endotoxin. Ca2+ signaling was examined in isolated bileducts from these animals, whereas ductular bicarbonate secretion was examined in isolated perfused livers. Confocal immunofluorescence was used to examine cholangiocyte InsP3R expression in human liver biopsy specimens. Results: Expression of the InsP3R was selectively lost from biliary epithelia after bileduct ligation or endotoxin treatment. As a result, Ca2+ signaling and Ca2+-mediated bicarbonate secretion were lost as well, although other components of the Ca2+ signaling pathway and adenosine 3′,5′-cyclic monophosphate (cAMP)-mediated bicarbonate secretion both were preserved. Examination of human liver biopsy specimens showed that InsP3Rs also were lost from bileduct epithelia in a range of human cholestatic disorders, although InsP3R expression was intact in noncholestatic liver disease. Conclusions: InsP3-mediated Ca2+ signaling in bileduct epithelia appears to be important for normal bile secretion in the liver, and loss of InsP3Rs may be a final common pathway for cholestasis. PMID:14517800

Intercellular communication among certain cell types can occur via ATP secretion, which leads to stimulation of nucleotide receptors on target cells. In epithelial cells, however, intercellular communication is thought to occur instead via gap junctions. Here we examined whether one epithelial cell type, hepatocytes, can also communicate via nucleotide secretion. The effects on cytosolic Ca2+ ([Ca2+]i) of mechanical stimulation, including microinjection, were examined in isolated rat hepatocytes and in isolated bileduct units using confocal fluorescence video microscopy. Mechanical stimulation of a single hepatocyte evoked an increase in [Ca2+]i in the stimulated cell plus an unexpected [Ca2+]i rise in neighboring noncontacting hepatocytes. Perifusion with ATP before mechanical stimulation suppressed the [Ca2+]i increase, but pretreatment with phenylephrine did not. The P2 receptor antagonist suramin inhibited these intercellular [Ca2+]i signals. The ATP/ADPase apyrase reversibly inhibited the [Ca2+]i rise induced by mechanical stimulation, and did not block vasopressin-induced [Ca2+]i signals. Mechanical stimulation of hepatocytes also induced a [Ca2+]i increase in cocultured isolated bileduct units, and this [Ca2+]i increase was inhibited by apyrase as well. Finally, this form of [Ca2+]i signaling could be elicited in the presence of propidium iodide without nuclear labeling by that dye, indicating that this phenomenon does not depend on disruption of the stimulated cell. Thus, mechanical stimulation of isolated hepatocytes, including by microinjection, can evoke [Ca2+]i signals in the stimulated cell as well as in neighboring noncontacting hepatocytes and bileduct epithelia. This signaling is mediated by release of ATP or other nucleotides into the extracellular space. This is an important technical consideration given the widespread use of microinjection techniques for examining mechanisms of signal transduction. Moreover, the evidence provided suggests a

We intended to investigate the clinicopathological features of intrahepatic intraductal papillary neoplasms of the bileduct (IPNB), especially their malignant features and post-resection prognosis. Forty-three patients who met the definition of IPNB and who underwent liver resection between January 2002 and June 2015 were selected from our institutional database of liver resection cases. The mean age was 63.3 ± 6.9 years and 24 were male. Hepatolithiasis was present in addition in 10 of the patients. Left- and right-sided hepatectomies and concurrent bileduct resection (BDR) were performed in 28, 15, and 10 patients, respectively; R0 resection was performed in 37 patients. The mean tumor diameter was 4.1 ± 2.2 cm. Histological tumor grade was low in 4 cases, intermediate in 6, and malignant in 33. There was no cancer-related recurrence or death in the 10 patients with low-grade or intermediate lesions. In the 33 patients with malignant lesions, rates of tumor recurrence and overall survival were 12.5 and 96.2 % at 1 year, 36.4 and 91.3 % at 3 years, and 47.0 and 68.8 % at 5 years, respectively. Multivariate analysis showed that R1 resection was the only prognostic factor for tumor recurrence and patient survival. BDR was performed in only 2 of 6 patients undergoing R1 resection. Intrahepatic IPNB is a rare type of biliary neoplasm that encompasses a histological spectrum ranging from benign disease to invasive malignancy. Long-term survival was anticipated after curative resection. R1 resection reduced survival outcomes; therefore, we suggest that concurrent BDR should be performed if the resection margin of the bileduct is not reliably free of neoplastic involvement. PMID:26873016

Biliary-enteric communications caused by duodenal ulcers are uncommon, and choledochoduodenal fistula (CDF) is by far the most common type. Usually in this situation, food material does not enter the common bileduct because the duodenal lumen is intact. Here, we report a case in which cholangitis occurred due to food materials impacted through a CDF. Duodenal obstruction secondary to duodenal ulcer prevented food passage into the duodenum in this case. Surgical management was recommended; however, the patient refused surgery because of poor general condition. Consequently, the patient expired with sepsis secondary to ascending cholangitis. PMID:26064830

Introduction Commonly encountered foreign bodies are remnants from surgical procedures and ingested materials. Rarely, the latter cause stone formation in the biliary tract. Case History We describe a 51-year-old female who underwent choledoduodenostomy and who presented with abdominal distension caused by multiple stones in the bileducts within the liver (hepatolithiasis) and an intact celery stalk. Hepatolithiasis was demonstrated by ultrasonography and computed tomography of the abdomen. The celery stalk was not confirmed until exploration of the biliary duct. Conclusions Here, we describe, for the first time, an intact, undigested celery stalk in the biliary tract which induced hepatolithiasis. We believe that choledochojejunostomy favoured reflux of the celery stalk from the duodenum into the biliary tract. PMID:27087342

Extrahepatic bileduct cancer (cholangiocarcinoma) has a poor prognosis. Since surgical resection is the only way to prolong the patient's life, it is of critical importance to correctly determine the extent of lesions. However, conventional pre-operative assessments have insufficient spatial resolution for determining the surgical margin. A fluorescent contrast agent might provide a more precise measure to identify anomalies in biliary surface, when combined with probe-based confocal laser endomicroscopy (pCLE). We have previously shown that 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG), a fluorescent derivative of L-glucose (fLG), is specifically taken up into spheroids consisting of cells showing heterogeneous nuclear-cytoplasm ratio, a feature of malignant cells in clinical settings. In addition, a combined use of 2-TRLG, a membrane-impermeable fLG, with 2-NBDLG visualized membrane integrity as well. We therefore explored in the present study the availability of the fLGs in vivo as a contrast agent for pCLE by using a hamster model of cholangiocarcinoma. Extrahepatic cholangiocarcinoma developed in mid common duct in ~20 % of the animals subjected to cholecystoduodenostomy with the ligation at the distal end of the common duct followed by injection of a carcinogen N-nitrosobis(2-oxopropyl)amine. After infusing bileduct with a solution containing 2-NBDLG and 2-TRLG, the lumen was surgically exposed and examined by pCLE. Fluorescence pattern characterized by bright spots and dark clumps was detected in the areas diagnosed with cholangiocarcinoma in later histopathology, whereas no such pattern was detected in control animals. These findings may form a basis for elucidating a potential availability of fLGs in imaging cholangiocarcinoma by pCLE. PMID:26842558

The clinical presentation, management and outcome of all patients with bileduct injury who presented to our tertiary care centre at various stages after cholecystectomy were analyzed. The patients were categorized into three groups: group A-patients in whom the injury was detected during cholecystectomy, group B-patients who presented within 2 weeks of cholecystectomy and group C-patients who presented after 2 weeks of cholecystectomy. Our team acted as rescue surgeons and performed 'on-table' repair for injuries occurring in another unit or in another hospital. Strasberg classification of bileduct injury was followed. In group A, partial and complete transections were managed by repair over T-tube and high hepaticojejunostomy, respectively. Patients in group B underwent endoscopic retrograde cholangiogram and/or magnetic resonance cholangiogram to evaluate the biliary tree. Those with intact common bileduct underwent endoscopic papillotomy and stenting in addition to drainage of intra-abdominal collection when present. For those with complete transection, early repair was considered if there was no sepsis. In presence of intra-abdominal sepsis an attempt was made to create controlled external biliary fistula. This was followed by hepatico jejunostomy at least after 3 months. Group C patients underwent hepaticojejunostomy at least 6 weeks after the injury. The outcome was graded into three categories: grade A-no clinical symptoms, normal LFT; grade B-no clinical symptoms, mild derangement of LFT or occasional episodes of pain or fever; grade C-pain, cholangitis and abnormal LFT; grade D-surgical revision or dilatation required. Fifty nine patients were included in the study and the distribution was group A-six patients, group B-33 patients and group C-20 patients. In group A, one patient with complete transection of the right hepatic duct (type C) and partial injury to left hepatic duct (LHD) underwent right hepaticojejunostomy and repair of the LHD over

We herein report a case of a 56-year-old man with IgG4-related sclerosing cholangitis (IgG4-SC) with no biliary stricture, but with a severely thickened bileduct wall. Contrast-enhanced computed tomography showed diffuse swelling of the pancreas and thickening of the common bileduct (CBD) wall with delayed enhancement. Obvious diffuse wall thickening of the CBD was observed on endoscopic ultrasonography. However, endoscopic retrograde cholangiography showed no biliary stricture in the CBD that had thickened. Although IgG4-SC has been classified by a stenotic lesion on cholangiography, we should be aware of some IgG4-SC cases showing only bileduct wall thickness without any biliary stricture. PMID:27301508

Intraductal papillary or tubular neoplasms of the bileduct have recently been proposed as one of the pre-invasive lesions of cholangiocarcinoma. Herein, a total of 50 cases of intraluminal polypoid neoplasms of the bileducts experienced in Khon Kaen University Hospital in Thailand were pathologically examined. These cases presumably had a history of infection of Opisthorchis viverrini. These neoplasms were histologically composed of high-grade intraepithelial neoplasm showing a tubular and/papillary pattern without invasion (20 cases), and with minimal and considerable invasion (15 and 15 cases, respectively). They were histologically classifiable into papillary type (10 cases), tubular type (20 cases) and papillotubular type (20 cases), and were phenotypically classifiable into gastric (17 cases), intestinal (17 cases) and pancreatobiliary types (16 cases). It was found that cases of papillary type and gastric or intestinal phenotype were less invasive, while those of tubular or papillotubular type and pancreatobiliary phenotype were more invasive. In conclusion, intraductal polypoid neoplasms in Thailand were well-differentiated papillary and/or tubular neoplasms including those with no or minimal invasion, and histological and phenotypic subclassifications seem to be useful for evaluation of the aggressive pathological behaviors of these neoplasms. PMID:26339398

Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver development; however, the molecular mechanisms regulating the phenotype of these cells have not been completely elucidated. Matrix metalloproteinase (MMP)-14 is a type I transmembrane proteinase regulating pericellular proteolysis of the extracellular matrix and is essential for the activation of several MMPs and cytokines. However, the physiological functions of MMP-14 in liver development are unknown. Here we describe a functional role for MMP-14 in hepatic and biliary differentiation of mouse hepatoblasts. MMP-14 was upregulated in cells around the portal vein in perinatal stage liver. Formation of bileduct-like structures in MMP-14-deficient livers was significantly delayed compared with wild-type livers in vivo. In vitro biliary differentiation assays showed that formation of cholangiocytic cysts derived from MMP-14-deficient hepatoblasts was completely impaired, and that overexpression of MMP-14 in hepatoblasts promoted the formation of bileduct-like cysts. In contrast, the expression of molecules associated with metabolic functions in hepatocytes, including hepatic nuclear factor 4α and tryptophan 2,3-dioxygenase, were significantly increased in MMP-14-deficient livers. Expression of the epidermal growth factor receptor and phosphorylation of mitogen-activated protein kinases were significantly upregulated in MMP-14-deficient livers. We demonstrate that MMP-14-mediated signaling in fetal hepatic progenitor cells promotes biliary luminal formation around the portal vein and negatively controls the maturation of hepatocytes. PMID:26724533

Objective Paucity of interlobular bileducts (PIBD), defined as absence or marked decrease in the number of interlobular bileducts, is one of the causes of neonatal cholestasis. Treatment includes treating the intractable pruritus caused by persistent cholestasis. PIBD can be part of a familial syndrome of cholestasis named Alagille syndrome (AGS). We report clinical status of a case series of Iranian patients with PIBD. Methods In this retrospective study, patients with cholestasis admitted to the pediatric gastroenterology ward in a referral hospital in Shiraz from January 2006 to January 2010 and underwent liver biopsy were evaluated. Clinical and paraclinical status of children with the pathologic diagnosis of PIBD was assessed. Findings Disease was presented in all jaundiced patients with aged in average 3 days at presentation. Seven patients had the criteria of AGS. Despite medical treatment, cholestasis was not controlled in 6 (28.6%) patients. Liver transplantation led to the survival of 5 patients while the other patient who did not undergo liver transplantation died at 2 months of age. One patient underwent peritoneal dialysis due to renal insufficiency and died at 9 months of age. After 1-5 years of follow-up, the mortality rate was 9.5%. Conclusion In patients with intractable cholestasis, only patients that underwent liver transplantation survived. Thus, the most important criterion for liver transplantation in neonatal PIBD is intractable cholestasis. This is the first report that shows AGS can result in neonatal-onset renal insufficiency. PMID:23550220

Alagille syndrome, a chronic hepatobiliary disease, is characterized by paucity of intrahepatic bileducts (IHBDs). To determine the impact of Notch signaling specifically on IHBD arborization we studied the influence of both chronic gain and loss of Notch function on the intact three-dimensional IHBD structure using a series of mutant mouse models and a resin casting method. Impaired Notch signaling in bi-potential hepatoblast progenitor cells (BHPCs) dose-dependently decreased the density of peripheral IHBDs, whereas activation of Notch1 results in an increased density of peripheral IHBDs. While Notch2 has a dominant role in IHBD formation there is also a redundant role for other Notch receptors in determining the density of peripheral IHBDs. Since changes in IHBD density do not appear to be due to changes in cellular proliferation of bileduct progenitors, we suggest that Notch plays a permissive role in cooperation with other factors to influence lineage decisions of BHPCs and sustain peripheral IHBDs. Conclusion There is a threshold requirement for Notch signaling at multiple steps, IHBD tubulogenesis and maintenance, during hepatic development that determines the density of three-dimensional peripheral IHBD architecture. PMID:20069650

Bileduct hamartomas (BHs), also called von Meyenburg complex (VMC), are benign biliary malformations that originate from disorganization of the small intrahepatic bileducts. This disorganization is often associated with the abnormal involution of embryonic ductal end plates in the liver. This is clinically significant, as the development of BHs can cause diagnostic confusion with liver metastases and small hepatocellular carcinoma (SHCC). Currently, we report a specific case of BHs and review the literature to better define and diagnose BHs. In the following case, a 37 year-old male bearing a lesion in his liver is presented and undergoes both radiological and pathological diagnosis. The lesion is preliminarily suspected to be a hepatic hemangioma by examination of conventional ultrasound (US), contrast enhanced ultrasound (CEUS), computerized tomographic scanning (CT) and magnetic resonance imaging (MRI). However, SHCC is suspected by follow-up analysis of US and CEUS, due to the patient’s background history of hepatitis B and growth of the lesion and a tumor-feeding vessel in BHs via CEUS. However, BHs are finally diagnosed by biopsy pathology under the guidance of ultrasound. Therefore, we believe pathology is imperative for correct diagnosis of BHs over other similar diseases when the imaging findings are atypical. Here we report the novel and unique detection of a tumor-feeding vessel, which mimicked SHCC strongly, during the course of CEUS. We also present a comprehensive review of the previous reported radiological examination related to BHs. PMID:26550237

Collection of 10 or more stones in the extrahepatic common bileduct causes lithiasic obstruction of the CBD, a fairly rare entity observed in less than 10% of cases of bileduct lithiasis. This study is based on 35 cases recorded over 10 years, including 60% in patients aged more than 75 years. Endoscopic treatment was attempted in 28% of patients and was totally successful in one case our of four only because of insufficient removal of obstruction after sphincterotomy. Surgery, either necessary (8 cases) or systematic (25 cases) combines cholecystectomy, choledocotomy and biliary fiberendoscopy for a complete treatment minimizing the risks of residual lithiasis. While biliodigestive anastomoses prevailed (58%) during the first years of this study, external biliary drainage was most often chosen during the last 5 years. This surgery in aged patients still entails high morbidity (25%) and considerable mortality (9%). Better efficacy may be provided in the future by the combination of fiberendoscopic means and of lithotrity for aged subjects at high surgical risks. PMID:1342650

We report a 54-year-old male patient with arteriovenous malformation located at the common bileduct and hereditary hemorrhagic telangiectasia. The patient was treated as gallstone pancreatitis at first. Three days after endoscopic nasobiliary drainage (ENBD) for biliary drainage to subside gallstone pancreatitis, hemobilia was drained from the ENBD tube and the serum hemoglobin level gradually decreased. Cholangioscopy and angiography revealed that hemobilia was due to a small arteriovenous malformation located at the common bileduct. Subsequently, the patient was successfully treated by endovascular intervention.

Extrahepatic bileduct (EBD) injury can happen during surgery. To repair a defect of the EBD and prevent postoperative biliary complications, a collagen membrane was designed. The collagen material was porous, biocompatible, and degradable and could maintain its shape in bile soaking for about 4 weeks. The goal was to induce rapid bileduct tissue regeneration. Twenty Chinese experimental hybrid pigs were used in this study and divided into a patch group and a control group. A spindle-shaped defect (20 mm × 6 mm) was made in the anterior wall of the lower EBD in the swine model, and then the defect was reconstructed using a collagen patch with a drainage tube and wrapped with greater omentum. Ultrasound was performed at 2, 4, 8, and 12 weeks postoperatively. Liver function tests and white blood cell count (WBC) were measured. Hematoxylin-eosin staining, cytokeratin 7 immunohistochemical staining, and Van Gieson's staining of EBD were used. The diameter and thickness of the EBD at the graft site were measured. There was no significant difference in liver function tests or WBC in the patch group compared with the control group. No evidence of leakage or stricture was observed, but some pigs developed biliary sludge or stone at 4 and 8 weeks. The drainage tube was lost within 12 weeks. The neo-EBD could withstand normal biliary pressure 2 weeks after surgery. Histological study showed the accessory glands and epithelial cells gradually regenerated at graft sites from 4 weeks, with increasing vessel infiltration and decreasing inflammation. The collagen fibers became regular with full coverage of epithelial cells. The statistical analysis of diameter and thickness showed no stricture formation at the graft site, but the EBD wall was slightly thicker than in the normal bileduct due to collagen fiber deposition. The structure of the neo-EBD was similar to that of the normal EBD. The collagen membrane patch associated with a drainage tube and wrapped with greater

We experienced three hepatectomies in patients with a history of bileduct-gastrointestinal (GI) tract anastomosis at the porta hepatis. Patient 1 had a history of pancreaticoduodenectomy for bileduct cancer. Because the third liver metastasis of cecal cancer postoperatively invaded the right kidney, after 5 courses of FOLFOX we performed partial resection of the liver (S6) and the right kidney using microwave pre-coagulation and a cavitron ultrasonic surgical aspirator (CUSA) without the Pringle method. Patient 2 had a history of splenectomy for congenital spherocytosis, cholecystectomy, choledocholithotomy, and bileduct duodenal anastomosis for hepatolithiasis. Partial (S5) liver resection was performed to treat hepatocellular carcinoma. Patient 3 had a history of bileduct resection and choledochojejunostomy for congenital cystic dilatation of the common bileduct. She had repeated episodes of cholangitis in the year following surgery. Extended liver segmental (S4) resection was performed to treat intrahepatic bileduct carcinoma. Bileduct jejunum anastomosis was performed, and the portal vein and the hepatic artery in the porta hepatis were exfoliated. Hepatectomy was performed using the Pringle method and a CUSA. Surgical procedures using various devices are necessary for hepatectomy in patients with a history of bileduct-GI tract anastomosis at the porta hepatis. PMID:25731231

Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bileduct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP) were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bileduct to the common hepatic duct. A bileduct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive) surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC). Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bileduct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient's poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas. PMID:24804133

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bileduct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bileduct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin

A canine experimental model for the anomalous arrangement of the pancreaticobiliary ducts (APBD) was made to investigate the effects of bile acids on carcinogenesis. Seven adult mongrel dogs underwent dorsal pancreatico-cholecystostomy to serve as a functional model for APBD, and six dogs underwent the same procedure with the pancreatic duct ligated as a control group. Bile from the gallbladder was taken 14 months after surgery for bile acid analysis by HPLC. DNA strand breaks in HeLa cells induced by the bile were also investigated in situ by nick translation method. As a result, the fraction of cholic acid tended to be lower, and that of deoxycholic acid slightly higher in APBD-dogs (N.S.). The ursodeoxycholic acid percentage in APBD-dogs significantly decreased compared with that in the control and normal dogs (p < 0.05). Extremely high frequency of DNA strand breaks was shown in only two out of seven APBD-dogs. In those two dogs, the cholic acid percentage decreased and that of deoxycholic acid increased extremely. These findings suggest that the alteration of the bile composition in APBD caused frequent DNA strand breaks and repair which might lead to gene mutation and biliary tract carcinoma. PMID:9395717

Renal sodium reabsorption and the concentrating and diluting abilities of the kidney were evaluated in the same trained mongrel dogs before and after chronic common bileduct ligation (BDL). Glomerular filtration rate (GFR) and CPAH were not altered by BDL. The natriuretic response to a standardized infusion of 0.45% solution of NaCl was markedly blunted by BDL (P < 0.01); calculated distal sodium delivery was significantly less in experiments after BDL than in control studies. Furthermore, the fractional reabsorption of sodium at the diluting segment for any given rate of distal delivery was enhanced by BDL. Similarly, CH2O/100 ml GFR for a given sodium delivery was higher after BDL than control values. Maximal urinary concentration (Uosm-max) was lower after BDL, and the mean Uosm-max for the whole group of animals was 60% of the control value (P < 0.001). Mean maximal TH2O/100 ml GFR after BDL was not different from control values; however, TcH2O/100 ml GFR for a given Cosm/100 ml GFR was lower after BDL in three dogs only. The sodium content of the inner part of renal medulla after BDL was significantly lower than the values obtained in control animals. The excretion of an oral water load in the conscious state was impaired after BDL; although all animals excreted hypotonic urine, urinary osmolality was usually higher after BDL than in control studies. Maximal urinary concentration and the excretion of an oral water load were not affected by sham operation. These studies demonstrate that chronic, common bileduct ligation is associated with (a) enhanced sodium reabsorption both in the proximal and diluting segments of the nephron, (b) a defect in attaining maximal urinary concentration, (c) diminished sodium content in the renal papilla, and (d) impaired excretion of a water load. The results suggest that decreased distal delivery of sodium may underlie the abnormality in the concentrating mechanism and in the inability to normally excrete a water load. In

A 30 year old man with von Hippel-Lindau syndrome presented with obstructive jaundice caused by a carcinoid tumour of the mid- and upper common bileduct. This association is probably causally related in view of the propensity for patients with von Hippel-Lindau syndrome to develop neuroendocrine tumours. Images Figure 1 Figure 2 PMID:2379881

Intraductal papillary neoplasm of bileduct (IPNB) is a papillary tumor covered by well-differentiated neoplastic epithelium with fine fibrovascular cores in the dilated bileducts. It reportedly shows similarities to intraductal papillary mucinous neoplasm of pancreas (IPMN), to various degrees. Herein, IPNB was pathologically analyzed by classifying 52 cases into 4 groups based on the histopathologic similarities to IPMN: group A (identical to IPMN, 19 cases), group B (similar to but slightly different from IPMN, 18 cases), group C (vaguely similar to IPMN, 5 cases), and group D (different from IPMN, 10 cases). In group A, intrahepatic and perihilar regions were mainly affected, most cases were of low/intermediate or high grade without invasion, and gastric type was the most common phenotype, followed by oncocytic and intestinal types. In groups C and D, perihilar and distal bileducts were affected, almost all cases were of high grade with invasion, and most of them were of intestinal and pancreatobiliary phenotypes. Most group B cases were of intestinal phenotype, and all were of high grade with or without invasion. In conclusion, these 4 groups of IPNB showed unique pathologic features and behaviors. Group A cases were less aggressive and shared many features with IPMN, whereas group C and D cases were more aggressive and mainly found in perihilar and distal bileducts. Group B resembling IPMN was intermediate between them. This classification may be useful in clinical practice and holds promise for a novel approach to analyze IPNB tumorigenesis. PMID:27067788

Summary Infantile cholestatic disorders arise in the context of progressively developing intrahepatic bileducts. Biliary atresia (BA), a progressive fibroinflammatory disorder of extra- and intrahepatic bileducts, is the most common identifiable cause of infantile cholestasis and the leading indication for liver transplantation in children. The etiology of BA is unclear, and while there is some evidence for viral, toxic, and complex genetic causes, the exclusive occurrence of BA during a period of biliary growth and remodeling suggests an importance of developmental factors. Interestingly, interferon-γ (IFNγ) signaling is activated in patients and in the frequently utilized Rhesus rotavirus mouse model of BA, and is thought to play a key mechanistic role. Here we demonstrate intrahepatic biliary defects and upregulated hepatic expression of IFNγ pathway genes caused by genetic or pharmacological inhibition of DNA methylation in zebrafish larvae. Biliary defects elicited by inhibition of DNA methylation were reversed by treatment with glucocorticoid, suggesting that the activation of inflammatory pathways was critical. DNA methylation was significantly reduced in bileduct cells from BA patients compared to patients with other infantile cholestatic disorders, thereby establishing a possible etiologic link between decreased DNA methylation, activation of IFNγ signaling, and biliary defects in patients. Conclusion: Inhibition of DNA methylation leads to biliary defects and activation of IFNγ-responsive genes, thus sharing features with BA, which we determine to be associated with DNA hypomethylation. We propose epigenetic activation of IFNγ signaling as a common etiologic mechanism of intrahepatic bileduct defects in BA. PMID:21319190

Aims. To investigate the effect of biliary stent placement without endoscopic sphincterotomy (EST) on common bileduct stones (CBDS) disappearance and the contribution of preserving the duodenal papilla function to reduce recurrence of CBDS. Methods. Sixty-six patients admitted for acute obstructive cholangitis due to CBDS who underwent biliary stent placement without EST for 2 years from March 2011 were evaluated retrospectively. The second endoscopic retrograde cholangiopancreatography (ERCP) was performed for treatment of CBDS 3 to 4 months after the first ERCP. We estimated the rate of stone disappearance at the time of second ERCP. Results. CBDS disappearance was observed in 32 (48.5%) of 66 patients. The diameter of the bileducts and the diameter of CBDS in patients with CBDS disappearance were significantly smaller than in those with CBDS requiring extraction (p = 0.007 and p < 0.001, resp.). Stone disappearance was evident when the diameter of bileducts and that of CBDS were <10 and 7 mm, respectively (p = 0.002). Conclusions. Short-term stent placement without EST eliminates CBDS while preserving duodenal papilla function and may be suitable for treating CBDS in patients with nondilated bileducts and small CBDS. PMID:27247568

Twenty-two cholangiograms of adults with congenital dilatation of the common bileduct were studied and analyzed. Diagnosis of this disease was established by endoscopic retrograde cholangiopancreaticography in nine patients, by percutaneous transhepatic cholangiography in two patients, and by operative cholangiography in 11 patients. All patients, except one with Caroli's disease, were classified as type I according to Alonso-Lej. An anomalous junction of the pancreaticobiliary ductal system (AJPBDS) was observed in 15 cases. In nine patients the common bileduct joined the main pancreatic duct, and in the remaining six patients, the pancreatic duct was noted to join the common bileduct. These anomalies are considered to be an important etiologic factor in the development of choledochal dilatation. Total cyst excision and hepaticojejunostomy in a Roux-en-Y fashion is recommended as the procedure of choice in those cases with AJPBDS. This is based on the high incidence of cholangitis and the high propensity to induce malignancy of cystic wall following simple drainage. Images Fig. 2. Fig. 3. Fig. 4. PMID:7055397

Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bileduct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients. PMID:25548506

Bileduct ligation (BDL)-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher plasma and hepatic ADMA levels, which may be due to increased hepatic protein arginine methyltransferase-1 and decreased dimethylarginine dimethylaminohydrolase expression. BDL rats also exhibit renal and brain damage characterized by increased tissue ADMA concentrations. The increased plasma ADMA levels and multiple organ damages seen here are also observed following multiple organ failures associated with critical illness. This review discusses the dysregulation of ADMA in major organs in BDL rats and the role of increased ADMA in multiple organ damages. PMID:24603538

Endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is not normally indicated for an obstructed right intrahepatic bileduct (IHBD). The technical feasibility and clinical efficacy of a novel technique of EUS-BD for right IHBD obstruction were evaluated. A total of 11 patients underwent drainage using either a left or a right biliary access route. The causes of obstructive jaundice were cholangiocarcinoma (n = 6), pancreatic cancer (n = 3), gastric cancer (n = 1), and colon cancer (n = 1). After placement of an uncovered metal stent to bridge the obstruction, a hepaticogastrostomy was completed using a covered stent. Mean procedure time was 33.9 ± 10.0 minutes. Technical and functional success were achieved in all patients, and no adverse events occurred. This novel method appears to be safe and effective for right IHBD obstruction. PMID:25264761

A foreign body is a rare cause of obstructive jaundice. We report a 19-year-old woman with jaundice caused by a surgical gauze in the common bileduct (CBD). Four yours earlier, she had undergone a cholecystectomy and drainage for hydatid disease of the liver. Her postoperative course was complicated by a biliary fistula that healed after 50 days. She now presented with obstructive jaundice of 2 weeks' duration. Magnetic resonance cholangiopancreatography (MRCP) showed a signal-void mass, consistent with a CBD stone. Surgical exploration of the CBD revealed a surgical gauze as the cause of the obstruction. To the best of our knowledge, this is the first case of a surgical gauze obstructing the CBD requiring surgical removal. PMID:16547681

We report the case of a 78-year-old male patient with obstructive jaundice due to a pancreatic head neoplasm. The patient's general condition did not permit an endoscopic approach and the presence of diffuse liver metastases prohibited hepatic puncture for percutaneous biliary drainage, therefore the transcolecystic transperitoneal approach was decided to be the safest decompression route. Through a gallbladder access, a Viabil-covered stent with a mesh extension was placed in the distal common bileduct, without complications. The patient died 8 months later without signs of stent dysfunction or necessity of reintervention. Transcholecystic transperitoneal access is a safe option when diffuse liver metastases prohibit the transhepatic approach, even in cases where placement of a covered stent is considered necessary.

Background and study aims: Current evidence supporting the efficacy of peroral cholangioscopy (POC) in the evaluation and management of difficult bileduct stones and indeterminate strictures is limited. The aims of this systematic review and meta-analysis were to assess the following: the efficacy of POC for the therapy of difficult bileduct stones, the diagnostic accuracy of POC for the evaluation of indeterminate biliary strictures, and the overall adverse event rates for POC. Patients and methods: Patients referred for the removal of difficult bileduct stones or the evaluation of indeterminate strictures via POC were included. Search terms pertaining to cholangioscopy were used, and articles were selected based on preset inclusion and exclusion criteria. Quality assessment of the studies was completed with a modified Newcastle-Ottawa Scale. After critical literature review, relevant outcomes of interest were analyzed. Meta-regression was performed to examine potential sources of between-study variation. Publication bias was assessed via funnel plots and Egger’s test. Results: A total of 49 studies were included. The overall estimated stone clearance rate was 88 % (95 % confidence interval [95 %CI] 85 % – 91 %). The accuracy of POC was 89 % (95 %CI 84 % – 93 %) for making a visual diagnosis and and 79 % (95 %CI 74 % – 84 %) for making a histological diagnosis. The estimated overall adverse event rate was 7 % (95 %CI 6 % – 9 %). Conclusions: POC is a safe and effective adjunctive tool with endoscopic retrograde cholangiopancreatography (ERCP) for the evaluation of bileduct strictures and the treatment of bileduct stones when conventional methods have failed. Prospective, controlled clinical trials are needed to further elucidate the precise role of POC during ERCP. PMID:27004242

The inflammatory cytokine IL-6 is essential for cell survival after liver injury. Bileduct epithelia (BDE) markedly upregulate IL-6 release after liver injury, but the mechanisms regulating this have not been defined. Purinergic signals induce multiple potent downstream effects in BDE, so the goals of this study were to determine whether extracellular ATP regulates BDE IL-6 transcription and to identify the molecular mechanisms regulating this process. Effects of extracellular nucleotides on IL-6 transcription in primary rat bileduct epithelia were assessed. The relative effects of cAMP and cytosolic calcium were determined by use of agonists and antagonists. The role of the cAMP response element (CRE) was determined by site-directed mutagenesis. We found that ATP potently upregulated IL-6 mRNA, and that the pharmacological profile for IL-6 upregulation was most consistent with the newly identified P2Y11 receptor. This occurred in a cAMP-dependent and calcium-dependent fashion. The effect of cAMP and calcium agonists on IL-6 promoter activity was synergistic, and mutation of the IL-6 CRE blocked upregulation by ATP. Taken together, these data show that extracellular ATP acts through a mechanism involving a rat P2Y receptor functionally related to the P2Y11 receptor, cAMP, and calcium signals and that the IL-6 promoter CRE to upregulate transcription of IL-6 in BDE. Since IL-6 has such critical importance in the liver, it is likely that this pathway is of great relevance to the understanding of hepatic response to injury. PMID:19136380

Obstruction of the common bileduct in a variety of clinical settings leads to cholestatic liver injury. An important aspect of this injury is hepatic inflammation, with neutrophils as the prominent cell type involved. However, the pathophysiologic role of the infiltrating neutrophils during cholestatic liver injury remains unclear. Therefore, we tested the hypothesis that neutrophils contribute to the overall pathophysiology by using bileduct-ligated (BDL) wild-type animals and mice deficient in the beta(2) integrin CD18. In wild-type animals, neutrophils were activated systemically as indicated by the increased expression of Mac-1 (CD11b/CD18) and L-selectin shedding 3 days after BDL. Histologic evaluation (48 +/- 10% necrosis) and plasma transaminase levels showed severe liver injury. Compared with sham-operated controls (< 10 neutrophils per 20 high-power fields), large numbers of neutrophils were present in livers of BDL mice (425 +/- 64). About 60% of these neutrophils had extravasated into the parenchyma. In addition, a substantial number of extravasated neutrophils were found in the portal tract. In contrast, Mac-1 was not up-regulated and plasma transaminase activities and the area of necrosis (21 +/- 9%) were significantly reduced in CD18-deficient animals. These mice had overall 62% less neutrophils in the liver. In particular, extravasation from sinusoids and portal venules (PV) was reduced by 91% and 47%, respectively. Immunohistochemical staining for chlorotyrosine, a marker of neutrophil-derived oxidant stress, was observed in the parenchyma of BDL wild-type but not CD18-deficient mice. In conclusion, neutrophils aggravated acute cholestatic liver injury after BDL. This inflammatory injury involves CD18-dependent extravasation of neutrophils from sinusoids and reactive oxygen formation. PMID:12883479

Purpose Cholecystectomy in patients with an intact gallbladder after endoscopic removal of stones from the common bileduct (CBD) remains controversial. We conducted a case-control study to determine the risk of recurrent CBD stones and the benefit of cholecystectomy for prevention of recurrence after endoscopic removal of stones from the CBD in Korean patients. Materials and Methods A total of 317 patients who underwent endoscopic CBD stone extraction between 2006 and 2012 were included. Possible risk factors for the recurrence of CBD stones including previous cholecystectomy history, bileduct diameter, stone size, number of stones, stone composition, and the presence of a periampullary diverticulum were analyzed. Results The mean duration of follow-up after CBD stone extraction was 25.4±22.0 months. A CBD diameter of 15 mm or larger [odds ratio (OR), 1.930; 95% confidence interval (CI), 1.098 to 3.391; p=0.022] and the presence of a periampullary diverticulum (OR, 1.859; 95% CI, 1.014 to 3.408; p=0.045) were independent predictive factors for CBD stone recurrence. Seventeen patients (26.6%) in the recurrence group underwent elective cholecystectomy soon after endoscopic extraction of CBD stones, compared to 88 (34.8%) in the non-recurrence group; the difference was not statistically significant (p=0.212). Conclusion A CBD diameter of 15 mm or larger and the presence of a periampullary diverticulum were found to be potential predictive factors for recurrence after endoscopic extraction of CBD stones. Elective cholecystectomy after clearance of CBD stones did not reduce the incidence of recurrent CBD stones in Korean patients. PMID:26632393

Abstract Hepatectomy is a safe and effective treatment for intrahepatic stones (IHSs). However, the resection plane for right-sided stones distributed within 2 segments is obstacle because of atrophy-hypertrophy complex formation of the liver and difficult dissection of segmental pedicle within the Glissonean plate by conventional approach. Thus, we devised segmental bileduct-targeted liver resection (SBDLR) for IHS, which aimed at completely resection of diseased bileducts. This study aimed to evaluate the outcomes of SBDLR for right-sided IHSs. From January 2009 to December 2013, 107 patients with IHS treated by SBDLR in our center were reviewed in a prospective database. Patients’ intermediate and long-term outcomes after SBDLR were analyzed. A total of 40 (37.4%) patients with localized right-sided stone and 67 (62.7%) patients with bilateral stones underwent SBDLR alone and SBDLR combined with left-sided hepatectomy, respectively. There was no hospital mortality of this cohort of patients. The postoperative morbidity was 35.5%. The mean intraoperative blood loss was 414 mL (range: 100–2500). Twenty-one (19.6%) patients needed red blood cells transfusion. The intermediate stone clearance rate was 94.4%; the final clearance rate reached 100% after subsequent postoperative cholangioscopic lithotomy. Only 2.8% patients developed stone recurrence in a median follow-up period of 38.3 months. SBDLR is a safe and effective treatment for right-sided IHS distributed within 2 segments. It is especially suitable for a subgroup of patients with bilateral stones whose right-sided stones are within 2 segments and bilateral liver resection is needed. PMID:26181559

Hepatectomy is a safe and effective treatment for intrahepatic stones (IHSs). However, the resection plane for right-sided stones distributed within 2 segments is obstacle because of atrophy-hypertrophy complex formation of the liver and difficult dissection of segmental pedicle within the Glissonean plate by conventional approach. Thus, we devised segmental bileduct-targeted liver resection (SBDLR) for IHS, which aimed at completely resection of diseased bileducts. This study aimed to evaluate the outcomes of SBDLR for right-sided IHSs. From January 2009 to December 2013, 107 patients with IHS treated by SBDLR in our center were reviewed in a prospective database. Patients' intermediate and long-term outcomes after SBDLR were analyzed. A total of 40 (37.4%) patients with localized right-sided stone and 67 (62.7%) patients with bilateral stones underwent SBDLR alone and SBDLR combined with left-sided hepatectomy, respectively. There was no hospital mortality of this cohort of patients. The postoperative morbidity was 35.5%. The mean intraoperative blood loss was 414 mL (range: 100-2500). Twenty-one (19.6%) patients needed red blood cells transfusion. The intermediate stone clearance rate was 94.4%; the final clearance rate reached 100% after subsequent postoperative cholangioscopic lithotomy. Only 2.8% patients developed stone recurrence in a median follow-up period of 38.3 months. SBDLR is a safe and effective treatment for right-sided IHS distributed within 2 segments. It is especially suitable for a subgroup of patients with bilateral stones whose right-sided stones are within 2 segments and bilateral liver resection is needed. PMID:26181559

Purpose: To compare the effectiveness of various means of stenting in patients with biliary obstruction caused by pancreatic cancer in a retrospective analysis. Methods: Sixty-two patients with biliary obstruction due to unresectable pancreatic cancer underwent biliary stenting. On the basis of the findings obtained by percutaneous transhepatic cholangiography(10 patients) and endoscopic retrograde cholangiography (52 patients),the site of obstruction was distal to the hilar confluence,predominantly especially in the middle to lower third of the common bileduct. Polyurethane-covered Wallstents (9 mm in diameter) we reinserted in 13 patients, while uncovered Wallstents (10 mm in diameter)were used in 10 patients and plastic stents (10 Fr and 12 Fr) were used in 39 patients. Results: Stenting was successful in 34 patients (87.2%) treated with plastic stents and in 22 patients(95.7%) treated with Wallstents. Effective biliary drainage was achieved in 32 out of 34 patients (94.1%) treated with plastic stents and in 21 out of 22 patients (95.5%) treated with Wallstents. The cumulative patency rate was significantly higher for the uncovered and covered Wallstents compared to plastic stents, but was not significantly higher for covered than for uncovered Wallstents. Stentocclusion occurred in 23 patients (70%; all by clogging) from the plastic stent group, in two patients (22%; by tumor ingrowth) from the uncovered Wallstent group, and in one patient (9%; by clogging) from the covered Wallstent group. The survival rate showed no significant difference among the three stent groups. Conclusion: The Wallstent is effective for long-term palliation in patients with obstruction caused by pancreatic cancer invading the middle to lower part of the common bileduct. The covered Wallstent can prevent tumor ingrowth, a problem with the uncovered Wallstent. However, it may be necessary to take measures to prevent the migration or clogging of covered Wallstents.

The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bileduct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations. PMID:23534919

AIM: To measure the common bileduct (CBD) diameter by magnetic resonance cholangiopancreatography (MRCP) in a large asymptomatic population and analyze its some affecting factors. METHODS: This study included 862 asymptomatic subjects who underwent MRCP. The CBD diameter was measured at its widest visible portion on regular end-expiration MRCP for all subjects. Among these 862 subjects, 221 volunteers also underwent end-inspiration MRCP to study the effect of respiration on the CBD diameter. The age, sex, respiration, body length, body weight, body mass index (BMI), portal vein diameter (PVD), length of the extrahepatic duct and CBD, cystic junction radial orientation and location were recorded. The subjects were divided into 7 groups according to age. All of the above factors were compared with the CBD diameter on end-expiration MRCP. RESULTS: Among the 862 subjects, the CBD diameter was 4.13 ± 1.11 mm (range, 1.76-9.45 mm) and was correlated with age (r = 0.484; P < 0.05), with a dilation of 0.033 mm per year. The upper limit of the 95% reference range was 5.95 mm, resulting in a reasonable upper limit of 6 mm for the asymptomatic population. Respiration and other factors, including sex, body length, body weight, BMI, PVD, length of the extrahepatic duct and CBD, cystic junction radial orientation and location, were not related to the CBD diameter. CONCLUSION: We established a reference range for the CBD diameter on MRCP for an asymptomatic population. The CBD diameter is correlated with age. Respiration did not affect the non-dilated CBD diameter. PMID:26753065

Secure reconstruction of multiple hepatic ducts that are severely damaged by tumor invasion or iatrogenic injury is a challenge. Failure of percutaneous or endoscopic biliary stenting requires lifelong placement of one or more percutaneous transhepatic biliary drainage (PTBD) tubes. For such difficult situations, we devised a surgical technique termed cluster hepaticojejunostomy (HJ), which can be coupled with palliative bileduct resection. The cluster HJ technique consisted of applying multiple internal biliary stents and a single wide porto-enterostomy to the surrounding connective tissues. The technique is described in detail in the present case report. Performing cluster HJ benefits from three technical tips as follows: making the multiple bileduct openings wide and parallel after sequential side-to-side unification; radially anchoring and traction of the suture materials at the anterior anastomotic suture line; and making multiple segmented continuous sutures at the posterior anastomotic suture line. Thus, cluster HJ with radial spreading anchoring traction technique is a useful surgical method for secure reconstruction of severely damaged hilar bileducts. PMID:27212993

Secure reconstruction of multiple hepatic ducts that are severely damaged by tumor invasion or iatrogenic injury is a challenge. Failure of percutaneous or endoscopic biliary stenting requires lifelong placement of one or more percutaneous transhepatic biliary drainage (PTBD) tubes. For such difficult situations, we devised a surgical technique termed cluster hepaticojejunostomy (HJ), which can be coupled with palliative bileduct resection. The cluster HJ technique consisted of applying multiple internal biliary stents and a single wide porto-enterostomy to the surrounding connective tissues. The technique is described in detail in the present case report. Performing cluster HJ benefits from three technical tips as follows: making the multiple bileduct openings wide and parallel after sequential side-to-side unification; radially anchoring and traction of the suture materials at the anterior anastomotic suture line; and making multiple segmented continuous sutures at the posterior anastomotic suture line. Thus, cluster HJ with radial spreading anchoring traction technique is a useful surgical method for secure reconstruction of severely damaged hilar bileducts. PMID:27212993

Endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been widely used as the alternative to EST along with endoscopic mechanical lithotripsy (EML) for the removal of large or difficult bileduct stones. Furthermore, EPLBD without EST was recently introduced as its simplified alternative technique. Thus, we systematically searched PubMed, Medline, the Cochrane Library and EMBASE, and analyzed all gathered data of EPLBD with and without EST, respectively, by using a single standardized definition, reviewing relevant literatures, published between 2003 and June 2013, where it was performed with large-diameter balloons (12-20 mm). The outcomes, including the initial success rate, the rate of needs for EML, and the overall success rate, and adverse events were assessed in each and compared between both of two procedures: "EPLBD with EST" and "EPLBD without EST". A total of 2511 procedures from 30 published articles were included in EPLBD with EST, while a total of 413 procedures from 3 published articles were included in EPLBD without EST. In the results of outcomes, the overall success rate was 96.5% in EPLBD with EST and 97.2% in EPLBD without EST, showing no significant difference between both of them. The initial success rate (84.0% vs 76.2%, P < 0.001) and the success rate of EPLBD without EML (83.2% vs 76.7%, P = 0.001) was significantly higher, while the rate of use of EML was significantly lower (14.1% vs 21.6%, P < 0.001), in EPLBD with EST. The rate of overall adverse events, pancreatitis, bleeding, perforation, other adverse events, surgery for adverse events, and fatal adverse events were 8.3%, 2.4%, 3.6%, 0.6%, 1.7%, 0.2% and 0.2% in EPLBD with EST and 7.0%, 3.9%, 1.9%, 0.5%, 0.7%, 0% and 0% in EPLBD without EST, respectively, showing no significant difference between both of them. In conclusion, recent accumulated results of EPLBD with or even without EST suggest that it is a safe and effective procedure for the

To explore the clinical effect of percutaneous transhepatic cholangioscopic lithotomy (PTCSL) combined with rigid choledochoscope and accurate positioning in the treatment of calculus of bileduct. This study retrospectively reviewed 162 patients with hepatolithiasis at the First Affiliated Hospital of Guangzhou Medical University between 2001 and 2013 were assigned to hard lens group or traditional PTCSL group. Compared with the traditional PTCSL, PTCSL with rigid choledochoscope can shorten the interval time which limit the PTCSL application. The operation time (45 vs 78, P=0.003), the number of operation (1.62 vs 1.97, P=0.031), and blood loss (37.8 vs 55.1, P=0.022) were better in hard lens group while the stone residual and complication had no significant differences. Rigid choledochoscope is a safe, minimally invasive and effective method in the treatment of bileduct stones. Accurate positioning method can effectively shorten operation process time. PMID:26629183

Ursodeoxycholic acid is the most widely used drug for treating cholestatic liver diseases. However, its effect on the male reproductive system alterations associated with cholestasis has never been studied. Thus, this study aimed to investigate the effect of ursodeoxycholic acid on cholestasis-induced alterations in the male reproductive system. Cholestasis was induced by bileduct ligation. Bileduct-ligated rats had higher cholestasis biomarkers and lower levels of testosterone, LH and FSH than did the Sham rats. They also had lower reproductive organs weights, and lower sperm motility, density and normal morphology than those of Sham rats. Histologically, these animals suffered from testicular tubular atrophy, interstitial edema, thickening of basement membranes, vacuolation, and depletion of germ cells. After ursodeoxycholic acid administration, cholestasis-induced structural and functional alterations were significantly ameliorated. In conclusion, ursodeoxycholic acid can ameliorate the reproductive complications of chronic cholestasis in male patients, which represents an additional benefit to this drug. PMID:25461907

Four patients with malignant obstruction of the common bileduct had been treated with uncovered Wallstents and suffered from a reobstruction after 2-13 months (mean 5.3 months). Repeat cholangiography revealed severe stenosis of the stent lumen caused by tumor ingrowth through the mesh. A Wallstent with a self-made polyurethane-cover was inserted through the uncovered stent in these patients. The four patients were followed for 3-13 months (mean 6.3 months) until death. There was good drainage with no evidence of recurrent obstruction in all patients. We conclude that a covered Wallstent may extend patency of stented bileducts, preventing tumor ingrowth in patients with neoplastic obstruction. Further observations are needed.

Background Currently, only x-ray fluoroscopy is available for visualization of the extrahepatic bileducts intraoperatively. We hypothesized that with an appropriate fluorophore and imaging system, invisible near-infrared (NIR) light could be used for image-guided procedures on the extrahepatic bileducts. Methods We quantified the performance of three 800 nm NIR fluorophores, differing primarily in their degree of hydrophilicity, for real-time imaging of the extrahepatic bileducts in rats and pigs: IR-786, indocyanine green (ICG), and the carboxylic form of IRDye™ 800CW (CW800-CA). The signal-to-background ratio (SBR) of the CBD relative to liver and pancreas was measured as a function of the dose of contrast agent, injection site, and kinetics using a previously described intraoperative NIR fluorescence imaging system. Bile samples were examined by high performance liquid chromatography tandem mass spectrometry (HPLC/MS) to determine the chemical form of fluorophores in bile. Results Non-sulfonated (IR-786) and di-sulfonated (ICG) NIR fluorophores had poor efficiency and kinetics of excretion into bile. Tetra-sulfonated CW800-CA, however, provided sensitive, specific, and real-time visualization of the extrahepatic bileducts after a single low-dose given either intraportally or intravenously via systemic vein. A SBR ≥2 provided sensitive assessment of extrahepatic bileduct anatomy and function, including the detection of millimeter-sized, radiolucent inclusions in pigs, for over 30 min post-injection. CW800-CA remained chemically intact after secretion into bile. Conclusion The combination of invisible NIR light and an IV injection of CW800-CA provides prolonged, real-time visualization of the extrahepatic bileducts, without ionizing radiation, and without changing the look of the surgical field. PMID:18571583

A radiolabeled probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue from three patients with chronic hepatitis B. The HBV genome was detected not only in infected hepatocytes but also in bileduct epithelial cells, endothelial cells, and smooth muscle cells. These findings extend the known host cell range for HBV, suggest new mechanisms of viral dissemination, and illustrate the usefulness of in situ hybridization in the study of pathogenesis of HBV infection.

Plasma kinetics of bromsulphalein (BSP) after a single injection into the bloodstream of the rat with total obstruction of the common bileduct was examined. The concentrations of BSP were determined colorimetrically. A monoexponential plus a general first-degree function in time with four unknown parameters was fitted. Two programs were developed for the Texas Instruments 59 programmable calculator to estimate the values of all the parameters by an iteration procedure. The programs executed at about twice normal speed. PMID:6617168

We encountered a very rare case of bileduct carcinoma associated with congenital biliary dilatation (CBD) in a 16-year-old female who was admitted to our hospital because of right upper abdominal pain and vomiting. Abdominal computed tomography demonstrated a cystic dilatation of the common bileduct measuring 7 cm in diameter and two enhanced tumors 4 cm in diameter located in the inferior bileduct and middle bileduct. Magnetic resonance cholangiopancreatography clearly demonstrated a cystic dilatation of the extrahepatic bileduct (Todani's CBD classification: type 4-A). Endoscopic retrograde cholangiopancreatography also revealed two tumors. Biopsy results of one of the tumors confirmed adenocarcinoma. Excision of the perihilar bileduct and subtotal stomach-preserving pancreaticoduodenectomy with dissection of the major lymph nodes were performed. A postoperative histopathologic examination revealed a well-differentiated tubular adenocarcinoma, which remained within the mucosal layer, and no lymph node metastasis was found. The postoperative course was uneventful, and the patient was discharged 10 days after surgery and has remained disease-free for 21 months. PMID:26943681

An extremely rare case of intrapancreatic bileduct metastasis from sigmoid colon adenocarcinoma is herein presented. Sigmoid colon cancer (T3, N0, M0, stage IIA) had been diagnosed and treated by sigmoidectomy in October 1993. In December 2002, a liver metastasis with intrabiliary growth was found, and this was treated by extended right hepatic lobectomy and caudate lobectomy with extrahepatic bileduct resection. In February 2014, intrapancreatic bileduct metastasis was found, and this was treated by subtotal stomach-preserving pancreatoduodenectomy. The intrapancreatic metastasis was judged to have arisen from cancer cell implantation, either by spontaneous shedding of cancer cells or as a complication of percutaneous transhepatic biliary drainage. Twelve months have passed since the last surgical intervention, and there has been no sign of local recurrence or distant metastasis. Differential diagnosis between intrahepatic cholangiocarcinoma and intrabiliary growth of a liver metastasis originating from colorectal adenocarcinoma is difficult but very important for determining the therapeutic strategy. Careful examination is needed to diagnose intrahepatic biliary dilatation, especially for patients with a history of carcinoma in the digestive tract and even if years have passed since curative resection of the digestive tract cancer. Aggressive surgical management for localized recurrence of a hepatic metastasis from colorectal adenocarcinoma may improve patient survival. PMID:26293132

'Single-sitting' laparoscopic cholecystectomy followed by endoscopic common bileduct clearance is emerging as a viable option for management of cholelithiasis and concomitant choledocholithiasis. The only disadvantage of the procedure is logistical since it requires co-ordination between two teams-the surgeons and the endoscopists. This limitation can be overcome in centres where both the procedures are performed by one team. With a considerable experience in endoscopy, we conducted a prospective study in a select group of patients to assess the feasibility of this single-sitting approach. The study included 38 patients with a radiological diagnosis of choledocholithiasis or jaundice at presentation. After laparoscopic cholecystectomy, the patients were turned prone and subjected to endoscopic retrograde cholangiogram, sphincterotomy and extraction of the common bileduct stone. The procedure was successful in 33 (87 %) of patients. The mean procedure time and hospital stay were 2 h, 20 min and 2 days, respectively. None of the patients had any major complications. We conclude that in a select group of patients, single-sitting laparoscopic cholecystectomy followed by endoscopic clearance of the common bileduct stone is safe and effective. PMID:26730094

Portal vein ligation (PVL) induces atrophy/hypertrophy complex (AHC). We hypothesised that simultaneous bileduct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. We established rat models of 90% BPL and 90% PVL and found that BPL was well-tolerated and significantly accelerated AHC. The enhanced BA retention in the intact liver promoted hepatocyte proliferation by promoting the activation of FXR signalling, while that in the ligated liver intensified caspase3-mediated apoptosis. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the bile acid pools of rats that underwent PVL could induce similar effects. Second-stage resection of posterior-caudate-lobe-spearing hepatectomy was performed 5 days after BPL (B-Hx), PVL (V-Hx) or sham (S-SHx), as well as whole-caudate-lobe-spearing hepatectomy 5 days after sham (S-Hx). The B-Hx group had the most favourable survival rate (93.3%, the S-SHx group 0%, the S-Hx group 26.7%, the V-Hx group 56.7%, P < 0.01) and the most sustained regeneration. We conclude that BPL is a safe and effective method, and the acceleration of AHC was bile acid-dependent. PMID:25678050

MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bileduct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy. PMID:26770318

MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bileduct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy. PMID:26770318

In recent years, the description of isolated bileduct dilatation has been increasingly observed in subjects with normal liver function tests and nonspecific abdominal symptoms, probably due to the widespread use of high-resolution imaging techniques. However, there is scant literature about the evolution of this condition and the impact of endoscopic ultrasound (EUS) in the diagnostic work up. When noninvasive imaging tests (transabdominal ultrasound, computed tomography or magnetic resonance cholangiopancreatography) fail to identify the cause of dilatation and clinical or biochemical alarm signs are absent, the probability of having biliary disease is considered low. In this setting, using EUS, the presence of pathologic findings (choledocholithiasis, strictures, chronic pancreatitis, ampullary or pancreatic tumors, cholangiocarcinoma), not always with a benign course, has been observed. The aim of this review has been to evaluate the prevalence of disease among non-jaundiced patients without signs of cytolysis and/or cholestasis and the assessment of EUS yield. Data point out to a promising role of EUS in the identification of a potential biliary pathology. EUS is a low invasive technique, with high accuracy, that could play a double cost-effective role: identifying pathologic conditions with dismal prognosis, in asymptomatic patients with negative prior imaging tests, and excluding pathologic conditions and further follow-up in healthy subjects. PMID:26191344

Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bileducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes +/- 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORT] with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98-months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone +/- 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent. Images FIG. 1. FIG. 1. PMID:1312319

Purpose. The recurrence of CBD stone is still observed in a considerable number of patients. The study was to evaluate the risk factors for recurrence of symptomatic CBD stone in patients who underwent cholecystectomy after the removal of CBD stone. Methods. The medical records of patients who underwent removal of CBD stone with subsequent cholecystectomy were reviewed. The risk factors for the recurrence of symptomatic CBD stone were compared between the recurrence and the nonrecurrence group. Results. The mean follow-up period was 40.6 months. The recurrence of symptomatic CBD stones was defined as the detection of bileduct stones no sooner than 6 months after complete clearance of CBD stones, based on symptoms or signs of biliary complication. 144 patients (68 males, 47.2%) were finally enrolled and their mean age was 59.8 (range: 26~86) years. The recurrence of CBD stone occurred in 15 patients (10.4%). The mean period until first recurrence was 25.9 months. The presence of type 1 or 2 periampullary diverticulum and multiple CBD stones were the independent risk factors. Conclusion. For the patients with type 1 or 2 periampullary diverticulum or multiple CBD stones, careful followup is needed for the risk in recurrence of symptomatic CBD stone. PMID:22991508

Fatigue is a common debilitating symptom in patients with primary biliary cirrhosis (PBC). The mechanism of fatigue is still poorly understood. However, it has been reported that levels of the steroid dehydroepiandrosterone sulphate (DHEAS) are reduced in plasma of patients with PBC, and substitutive therapy has been suggested to improve fatigue symptoms experienced during the course of this disease. In this study, we tested the effect of DHEAS on whole body fatigue in rats following bileduct ligation (BDL). Fatigue was estimated by the time spent on an electrified grid as a result of falling off a treadmill and by performance of rats on an infrared beam monitor which allows the assessment of travelled distance and stereotypic movement activities. On day 5 after BDL surgery, cholestatic rats exhibited increased whole body fatigue as reflected by significantly increased time spent on the electrified grid, reduced travelled distance and reduced stereotypic movements. Administration of 5 mg kg(-1) of DHEAS to BDL rats for three consecutive days significantly normalized their behaviour. Fatigue scores were also found to be reduced in cirrhotic rats 4 weeks after BDL surgery, and DHEAS treatment for 3 days reduced fatigue scores at this stage. Dehydroepiandrosterone sulphate treatment was sufficient to increase brain levels of DHEAS in the BDL rats in a manner that is significantly and highly correlated with those of plasma DHEAS and brain dehydroepiandrosterone (DHEA). Substitutive therapies with DHEAS or DHEA could represent novel approaches in the management of fatigue due to cholestasis-induced liver failure. PMID:19594690

Platycodin D (PD) is the major triterpene saponin in the root of Platycodon grandiflorum. The aim of the present study was to evaluate the protective effects of PD on bileduct ligation (BDL)-induced cholestasis in mice. Mice were allocated to five groups: sham, BDL alone, and BDL with PD treatment at 1, 2, and 4mg/kg. PD was administered to the mice for 28 consecutive days after the BDL operation. PD treatment of BDL-operated mice decreased serum alanine aminotransferase, serum aspartate aminotransferase, and total bilirubin levels by up to 37%, 31%, and 41%, respectively, in comparison with the levels in mice that underwent BDL alone. PD treatment attenuated oxidative stress, as evidenced by an increase in anti-oxidative enzyme levels glutathione and superoxide dismutase together with a decrease in lipid peroxidation and oxidative stress indices levels of malondialdehyde and nitric oxide. Histopathological studies further confirmed the protective effects of PD on cholestasis-induced hepatic injury and liver fibrosis in mice. In addition, nuclear factor-kappa B and inducible nitric oxide synthase levels significantly decreased after PD treatment, as did the levels of hepatocyte apoptosis. Taken together, these results suggest that PD treatment might be beneficial in cholestasis-induced hepatotoxicity. PMID:23116642

Background: Training models in laparoscopic surgery allow the surgical team to practice procedures in a safe environment. We have proposed the use of a 4-task, low-cost inert model to practice critical steps of laparoscopic common bileduct exploration. Methods: The performance of 3 groups with different levels of expertise in laparoscopic surgery, novices (A), intermediates (B), and experts (C), was evaluated using a low-cost inert model in the following tasks: (1) intraoperative cholangiography catheter insertion, (2) transcystic exploration, (3) T-tube placement, and (4) choledochoscope management. Kruskal-Wallis and Mann-Whitney tests were used to identify differences among the groups. Results: A total of 14 individuals were evaluated: 5 novices (A), 5 intermediates (B), and 4 experts (C). The results involving intraoperative cholangiography catheter insertion were similar among the 3 groups. As for the other tasks, the expert had better results than the other 2, in which no significant differences occurred. The proposed model is able to discriminate among individuals with different levels of expertise, indicating that the abilities that the model evaluates are relevant in the surgeon's performance in CBD exploration. Conclusions: Construct validity for tasks 2 and 3 was demonstrated. However, task 1 was no capable of distinguishing between groups, and task 4 was not statistically validated. PMID:22906323

AIM: To evaluate the efficacy of peripheral portal vein (PV)-oriented non-dilated bileduct (BD) puncture for percutaneous transhepatic biliary drainage (PTBD). METHODS: Thirty-five patients with non-dilated BDs underwent PTBD for the management of various biliary disorders, including benign bilioenteric anastomotic stricture (n = 24), BD stricture (n = 5) associated with iatrogenic BD injury, and postoperative biliary leakage (n = 6). Under ultrasonographic guidance, percutaneous transhepatic puncture using a 21-G needle was performed along the running course of the peripheral targeted non-dilated BD (preferably B6 for right-sided approach, and B3 for left-sided approach) or along the accompanying PV when the BD was not well visualized. This technique could provide an appropriate insertion angle of less than 30° between the puncture needle and BD running course. The puncture needle was then advanced slightly beyond the accompanying PV. The needle tip was moved slightly backward while injecting a small amount of contrast agent to obtain the BD image, followed by insertion of a 0.018-inch guide wire (GW). A drainage catheter was then placed using a two-step GW method. RESULTS: PTBD was successful in 33 (94.3%) of the 35 patients with non-dilated intrahepatic BDs. A right-sided approach was performed in 25 cases, while a left-sided approach was performed in 10 cases. In 31 patients, the first PTBD attempt proved successful. Four cases required a second attempt a few days later to place a drainage catheter. PTBD was successful in two cases, but the second attempt also failed in the other two cases, probably due to poor breath-holding ability. Although most patients (n = 26) had been experiencing cholangitis with fever (including septic condition in 8 cases) before PTBD, only 5 (14.3%) patients encountered PTBD procedure-related complications, such as transient hemobilia and cholangitis. No major complications such as bilioarterial fistula or portal thrombosis were

Background Anomalous biliary opening especially the presence of the ampulla of Vater in the duodenal bulb is a very rare phenomenon. We report clinical implications, laboratory and ERCP findings and also therapeutic approaches in 53 cases. Methods The data were collected from the records of 12.158 ERCP. The diagnosis was established as an anomalous opening of the common bileduct (CBD) into the duodenal bulb when there is an orifice observed in the bulb with the absence of a papillary structure at its normal localization and when the CBD is visualized by cholangiography through this orifice without evidence of any other opening. Results A total of 53 cases were recruited. There was an obvious male preponderance (M/F: 49/4). Demographic data and ERCP findings were available for all, but clinical characteristics and laboratory findings could be obtained from 39 patients with full records. Thirty – seven of 39 cases had abdominal pain (95%) and 23 of them (59%) had cholangitis as well. Elevated AP and GGT were found in 97.4% (52/53). History of cholecystectomy was present in 64% of the cases, recurrent cholangitis in 26% and duodenal ulcer in 45%. Normal papilla was not observed in any of the patients and a cleft-like opening was evident instead. The CBD was hook shaped at the distal part that opens to the duodenal bulb. Pancreatic duct (PD) was opening separately into the bulb in all the cases when it was possible to visualize. Dilated CBD in ERCP was evident in 94% and the CBD stone was demonstrated in 51%. PD was dilated in four of 12 (33%) cases. None of them has a history of pancreatitis. Endoscopically, Papillary Balloon Dilatation instead of Sphincterotomy carried out in 19 of 27 patients (70%) with choledocholithiazis. Remaining eight patients had undergone surgery (30%). Clinical symptoms were resolved with medical treatment in 16(32%) patients with dilated CBD but no stone. Perforation and bleeding were occurred only in two patients, which stones extracted

Purpose: The goal of this study was to determine the role of radiotherapy after curative-intent surgery in the management of extrahepatic bileduct (EHBD) cancers. Methods and Materials: From 1997 through 2005, 78 patients with EHBD cancer were surgically staged. These patients were stratified by the absence of adjuvant radiation (n = 47, group I) versus radiation (n = 31, group II) after resection. Pathology examination showed 27 cases in group I and 20 cases in group II had microscopically positive resection margins. The patients in group II received 45 to 54 Gy of external beam radiotherapy. The primary endpoints of this study were overall survival, disease-free survival, and prognostic factors. Results: There were no differences between the 5-year overall survival rates for the two groups (11.6% in group I vs. 21% in group II). However, the patients with microscopically positive resection margins who received adjuvant radiation therapy had higher median disease-free survival rates than those who underwent surgery alone (21 months vs. 10 months, respectively, p = 0.042). Decreasing local failure was found in patients who received postoperative radiotherapy (61.7% in group I and 35.6% in group II, p = 0.02). Outcomes of the patients with a positive resection margin and lymph node metastasis who received postoperative radiation therapy were doubled compared to those of patients without adjuvant radiotherapy. Resection margin status, lymph node metastasis, and pathology differentiation were significant prognostic factors in disease-free survival. Conclusions: Adjuvant radiotherapy might be useful in patients with EHBD cancer, especially for those patients with microscopic residual tumors and positive lymph nodes after resection for increasing local control.

Tetrathiomolybdate (TM), a potent copper-chelating drug, was initially developed for the treatment of Wilson’s disease. Our working hypothesis is that the fibrotic pathway is copper-dependent. Because biliary excretion is the major pathway for copper elimination, a bileduct ligation (BDL) mouse model was used to test the potential protective effects of TM. TM was given in a daily dose of 0.9 mg/mouse by means of intragastric gavage 5 days before BDL. All the animals were killed 5 days after surgery. Plasma liver enzymes and total bilirubin were markedly decreased in TM-treated BDL mice. TM also inhibited the increase in plasma levels of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 seen in BDL mice. Cholestatic liver injury was markedly attenuated by TM treatment as shown by histology. Hepatic collagen deposition was significantly decreased, and it was paralleled by a significant suppression of hepatic smooth muscle α-actin and fibrogenic gene expression in TM-treated BDL mice. Although the endogenous antioxidant ability was enhanced, oxidative stress as shown by malondialdehyde and 4-hydroxyalkenals, hepatic glutathione/oxidized glutathione ratio, was not attenuated by TM treatment, suggesting the protective mechanism of TM may be independent of oxidative stress. In summary, TM attenuated BDL-induced cholestatic liver injury and fibrosis in mice, in part by inhibiting TNF-α and TGF-β1 secretion. The protective mechanism seems to be independent of oxidative stress. Our data provide further evidence that TM might be a potential therapy for hepatic fibrosis. PMID:18299419

Background: To compare long term results of laparoscopic and endoscopic exploration of common bileduct, to assess post-procedure quality of life. Materials and Methods: From September 1992 to August 2003, we performed 4058 cholecystectomies, out of which 479 (11.80%) patients had choledocholithiasis. There were 163 males and 316 females. Mean age was 63.65 ± 5.5 years. These patients were put in two groups. In the first group of 240 patients, a majority of patients underwent two-stage procedures. ERCP/ES was performed in 210 (87.50%) cases. In the second group of 239 patients, a majority of patients underwent single-stage procedures. ERCP/ES was done in 32 (13.38%) cases. Results: Mortality was zero in both groups. Morbidity was 15.1% in first group and 7.5% in second group. Mean hospital stay was 11.7 ± 3.2 days in first group and 6.2 ± 2.1 days in second group. Average operative time was 95.6 ± 20 minutes in first group and 128.4 ± 32 minutes in second group. Completed questionnaires received from 400 (83.50%) patients revealed better long-term results in the second group. Clinical features of low-grade cholangitis were seen in 20% of patients who underwent ES. Hence the post-procedure quality of life in patients who underwent single-stage procedures was definitely much better, because of minimal damage of sphincter of Oddi. Conclusions: Single-stage laparoscopic operations provide better results and shorter hospital stay. Damage to sphincter of Oddi should be minimal, to avoid long-term low-grade cholangitis. In young patients, the operation of choice should be single-stage laparoscopic procedure with absolutely no damage to sphincter of Oddi. PMID:21170222

Backgrounds/Aims Laparoscopic treatment of patients with choledocholithiasis and cholangitis is challenging due to mandatory recovery of the biliary drainage and clearance of the common bileduct (CBD). The aim of our study was to assess postoperative course of cholangitis and biliary sepsis after laparoscopic clearance of the CBD in emergently admitted patients with choledocholithiasis and cholangitis. Methods Emergently admitted patients who underwent laparoscopic clearance of the CBD were included prospectively and stratified in 2 groups i.e., cholangitis positive (CH+) or negative (CH-) group. Patient demographics, comorbidities, preoperative imaging data, inflammatory response, surgical intervention, complication rate and outcomes were compared between groups. Results Ninety-nine of a total 320 patients underwent laparoscopic clearance of the CBD, of which, 60 belonged to the acute cholangitis group (CH+) and 39 to the cholangitis negative group (CH-). Interventions were done on average 4 days after admission, operation duration was 95-105 min, and the conversion rate was 3-7% without differences in the groups. Preoperative inflammatory response was markedly higher in the CH+ group. Inflammation signs on intraoperative choledochoscopy were more evident in patients with cholangitis. Postoperative inflammatory response did not differ between the groups. The overall complication rate was 8.3% and 5.1%, respectively. Laparoscopic clearance of the CBD resulted in 1 lethal case (CH+ group), resulting in 1% mortality rate and a similar 12-month readmission rate. Conclusions Single-stage laparoscopic intraoperative US and choledochoscopy-assisted clearance of the CBD is feasible in emergently admitted patients with choledocholithiasis and cholangitis. PMID:27212991

Background Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bileduct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches. Methods Eight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses. Results We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-α and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group. Conclusions We constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome. PMID:24733017

There is accumulating evidence that the renin-angiotensin system (RAS) is involved in hepatic inflammation and fibrogenesis. Garlic was found to lower the activity of the angiotensin converting enzyme (ACE) in the serum of rats in a diabetic model. We examined the effect of an aqueous garlic extract (AGE) on the ACE activity, cholestasis-induced liver fibrosis, and associated renal dysfunction in comparison with the effect of the standard drug enalapril. Both AGE and enalapril were administered orally for six weeks starting from the third day after bileduct ligation (BDL). BDL significantly increased the serum activities of liver enzymes, serum lactate dehydrogenase (LDH) activity, an indicator of liver cell death, serum total bilirubin (TB) level, liver myeloperoxidase (MPO) activity, and liver malondialdehyde (MDA) content. BDL was associated with elevation of serum urea and creatinine levels indicating renal dysfunction. BDL also caused an increase in the transcript levels of the genes coding for tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1), and matrix metalloproteinase-13 (MMP-13), a collagenase, in liver tissues. A significant decrease in hepatic reduced glutathione (GSH) was observed in BDL rats, while serum ACE activity was increased. Both AGE and enalapril counteracted all these deleterious changes, with the exception that only AGE reduced the MPO activity. These findings suggest that AGE possesses hepato- and renoprotective properties, similar to enalapril, probably by modulating the levels of proteins such as TNF-alpha, TGF-beta1 and MMP-13, and involving a reduction of ACE and of oxidative stress. PMID:24873034

AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bileduct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection. PMID:27358675

Summary Multiple organ failure is frequently associated with acute pancreatitis (AP). Our aim was to study pulmonary, hepatic and renal complications developed in the course of AP experimentally induced in rats by bile-pancreatic duct obstruction (BPDO), differentiating the complications caused by AP itself, from those directly caused by bileduct obstruction (BDO), after ligating the choledocus. N-acetylcysteine (NAC) was administered as a therapeutic approach. Myeloperoxidase activity revealed neutrophil infiltration in lungs from 12 h after BDO, even if AP was not triggered. Lactate dehydrogenase (LDH) activity indicated hepatocyte death from 48 h after BDO, and from 24 h following BPDO-induced AP onwards, an effect delayed until 48 h by NAC treatment. Rats with single cholestasis (BDO) and rats with BPDO-induced AP showed a significant increase in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin concentration from 12 h onwards, whose values were reduced by NAC treatment at early BPDO. No renal failure was found during 120 h of bile-pancreatic obstruction. Our results showed lung and liver impairment as a result of BDO, even if AP does not develop. Pancreatic damage and extrapancreatic complications during AP induced by BPDO were palliated by NAC treatment. PMID:17877536

The characteristics of sites of intramural cancer spread were examined by comparing the intraductal ultrasonography (IDUS) and wall thickening findings at sites of intramural cancer spread and non-spread, in patients with malignant bileduct stenosis who had undergone percutaneous transhepatic biliary drainage (PTBD). The subjects were ten patients with extrahepatic bileduct cancer, two with pancreatic cancer, one with cancer of the gallbladder, and one with cancer of the papilla of Vater who underwent preoperative IDUS. From these patients, 50 IDUS slices were examined with a congruent relationship with the histologic section of resected tissue. The maximum thickening, minimum thickening, maximum/minimum thickening ratio, and form factor of the medial and lateral margins of the medial hypoechoic layer were determined using diagnostic imaging, and the results were compared at sites of cancer spread and non-spread. Twelve slices were obtained from the site of stenosis, 14 from sites of cancer spread, and 24 from non-spread sites. The maximum thickening, minimum thickening, and maximum/minimum thickening ratio differed significantly between the sites of spread and the non-spread. The absolute values for wall thickening are useful for diagnosing the presence of intramural spread in patients with malignant biliary duct stenosis. PMID:18493560

Ectopic opening of the pancreatic and bileducts (EOPBD) into the duodenal bulb is an extremely rare congenital anomaly with unknown clinical implications. We presented a case of gallbladder cancer with EOPBD into the duodenal bulb. A 57-year-old male was referred to our hospital with intermittent right upper abdominal pain. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed individual EOPBD into the duodenal bulb with no papillary structure, and a focal nodular lesion in the gallbladder. A follow-up abdominal computed tomography scan 9 months later revealed a slight increase in the size of the fundal nodule, which was suspected as gallbladder cancer. An intraoperative frozen biopsy identified the nodular lesion as adenocarcinoma involving the cystic duct, and the patient underwent radical cholecystectomy including bileduct resection with hepaticojejunostomy. EOPBD is an extremely rare condition that can be associated with gallbladder malignancy as well as benign disease. Clinicians should follow up carefully and consider surgical treatment for suspected malignant lesions. PMID:26379734

Roux-en-Y hepaticojejunostomy anastomosis is the treatment of choice for common hepatic duct injury type E2. It has been performed laparoscopically with the advancement of laparoscopic skill. Recently, a telemanipulative robotic surgical system was introduced, providing laparoscopic instruments with wrist-arm technology and 3-dimensional visualization of the operative field. We present a case of 36-year-old female patient who had undergone elective cholecystectomy 2 mo ago for gall stones and had a common bileduct injury during surgery. As the stricture was old and complete it could not be tackled endoscopically. We did a laparoscopic assisted adhesiolysis followed by robotic Roux-en-Y hepaticojejunostomy. No intraoperative complications or technical problems were encountered. Postoperative period was uneventful and she was discharged on the 4th postoperative day. At follow-up, she is doing well without evidence of jaundice or cholangitis. This is the first reported case of robotic hepaticojejunostomy following common bileduct injury. The hybrid technique gives the patient benefit of laparoscopic adhesiolysis and robotic suturing. PMID:25684934

We report two cases of cystic neoplasm of the liver with mucinous epithelium in which both ovarian-like stroma and bileduct communication were absent. The first case was a 41-year-old woman. She underwent right trisegmentectomy due to a multilocular cystic lesion, 15 cm in diameter, with papillary nodular components in the medial segment and right lobe. Histologically, arborizing papillae were seen in the papillary lesion. The constituent neoplastic cells had sufficient cytoarchitectural atypia to be classified as high-grade dysplasia. The second case was a 60-year-old woman. She underwent left lobectomy due to a unilocular cystic lesion, 17 cm in diameter, in the left lobe. Histologically, the cyst wall was lined by low columnar epithelia with slight cellular atypia. In both cases, neither ovarian-like stroma nor bileduct communications were found throughout the resected specimen. According to the most recent World Health Organization (WHO) classification in 2010, cystic tumors of the liver with mucinous epithelium are classified as mucinous cystic neoplasms when ovarian-like stromata are found, and as intraductal papillary neoplasm of bileduct when bileduct communication exists. Therefore, we diagnosed the cystic tumors as 'biliary cystadenoma' according to the past WHO classification scheme from 2000. We believe that the combined absence of both ovarian-like stroma and bileduct communication is possible in mucinous cystic tumors of the liver. Herein, we have described the clinicopathologic features of the two cases and reviewed past cases in the literature. PMID:25047921

Purpose. To assess the feasibility of percutaneous transhepatic biliary drainage (PTBD) for the treatment of postsurgical biliary leaks in patients with nondilated intrahepatic bileducts, its efficacy in restoring the integrity of bileducts, and technical procedures to reduce morbidity. Methods. Seventeen patients out of 936 undergoing PTBD over a 20-year period had a noncholestatic liver and were retrospectively reviewed. All patients underwent surgery for cancer and suffered a postsurgical biliary leak of 345 ml/day on average; 71% were in poor condition and required permanent nutritional support. An endoscopic approach failed or was excluded due to inaccessibility of the bileducts. Results. Established biliary leaks and site of origin were diagnosed an average of 21 days (range 1-90 days) after surgery. In all cases percutaneous access to the biliary tree was achieved. An external (preleakage) drain was applied in 7 cases, 9 patients had an external-internal fistula bridging catheter, and 1 patient had a percutaneous hepatogastrostomy. Fistulas healed in an average of 31 days (range 3-118 days ) in 15 of 17 patients (88%) following PTBD. No major complications occurred after drainage. Post-PTBD cholangitis was observed in 6 of 17 patients (35%) and was related to biliary sludge formation occurring mostly when drainage lasted >30 days and was of the external-internal type. Median patient survival was 17.7 months and in all cases the repaired biliary leaks remained healed. Conclusions. PTBD is a feasible, effective, and safe procedure for the treatment of postsurgical biliary leaks. It is therefore a reliable alternative to surgical repair, which entails longer hospitalization and higher costs.

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bileduct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bileduct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bileduct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.

Objective: To evaluate the effects of intravenously infused lidocaine on analgesia and gastrointestinal function of patients receiving laparoscopic common bileduct exploration. Methods: Seventy-eight patients with cholelithiasis were randomly divided into a treatment group and a control group (n=39) that all had laparoscopic common bileduct exploration. The treatment group was intravenously infused with 1.5 mg/kg lidocaine by using a venous pump under anesthesia induction at the speed of 2 mg·kg-1 ·h-1 until the end of surgery, while the control group was given normal saline with the same volume. Results: All patients successfully completed the surgery, with similar surgical time, incision length and intraoperative blood loss. The required lidocaine concentrations of the treatment group were 2.64±1.23 μg/ml, 1.14±0.4 μg/ml and 0.93±0.32 μg/ml respectively 2 hour, 12 hour and 48 hour after surgery. Pain score of the treatment group, which was significantly lower than that of the control group at the postoperative 2 hour (P<0.05), was similar to those of the control group at the postoperative 12 hour and 48 hour. With extended time, the pain score significantly decreased (P<0.05). The treatment group had significantly shorter first anal exhaust time and first defecation time than those of the control group (P<0.05). Adverse reactions, such as nausea and vomiting, dizziness, headache, subcutaneous emphysema and fat liquefaction of incision, occurred similarly in the two groups, which were alleviated by symptomatic treatment. Conclusion: Laparoscopic common bileduct exploration is a promising minimally invasive surgery for patients with cholelithiasis, during which intravenously infused lidocaine can rapidly recover the gastrointestinal function and exert short-term analgesic effects, with mild adverse reactions also. PMID:26648989

Background: Progression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM). Matrix-metalloproteinases (MMP) cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes). The levels of these neo-epitopes might reflect the stage of liver fibrosis and may allow monitoring of anti-fibrotic therapies. Here we analyzed these neo-epitopes as read-out for a liver directed therapy with statins. Methods: Bileduct ligation (BDL) was performed on wild type rats, which received atorvastatin (15 mg/kg*d) for 1 week starting at 1, 2, 3, 4 and 5 weeks after BDL (T1–T5), while controls remained untreated. Hepatic fibrosis was analyzed by immunohistochemistry and hepatic hydroxyproline content. TGFβ levels were measured by RT-PCR. Proteolytic activity of MMP-2 was examined by zymography. Levels of degradation MMP driven type I, III, IV and VI collagen degradation (C1M, C3M, C4M, and C6M) and type III and IV collagen formation (PRO-C3 and P4NP7S) markers were assessed by specific ELISAs in serum probes. Results: Serum markers of ECM neo-epitopes reflected significantly the deposition of ECM in the liver and were able to distinguish between early (T1–T3) and severe fibrosis (T4–T5). Statin treatment resulted in reduction of neo-epitope markers, especially when therapy was started in the stage of severe fibrosis (T4–T5). Furthermore, these markers correlated with hepatic expression of profibrotic cytokines TGFβ1 and TGFβ2. Formation markers of type III and IV collagen (PRO-C3 and P4NP7S) and degradation markers C4M and C6M correlated significantly with hepatic MMP-2 activity in rats with severe fibrosis. Conclusion: Determination of ECM remodeling turnover markers in serum allowed a distinction between mild and severe fibrosis. With respect to statin therapy, the markers may serve as read-out for efficacy of anti-fibrotic treatment. PMID:23908632

Electromagnetically generated extracorporeal shock waves (without waterbath) were applied after intravenous premedication with 10-15 mg diazepam and 100 mg tramadol in the treatment of 33 patients (aged 32 to 91 years) with multiple intrahepatic stones (n = 4) or huge common bileduct stones (n = 29, 18-30 mm in diameter), which could not be removed by conventional endoscopy. Stone disintegration was achieved in 70% of common bileduct stones and in all intrahepatic concrements after 800-7500 discharges, which were applied during one (n = 21), two (n = 6) or three sessions (n = 6). Apart from mild fleabite-like petechiae at the side of shock wave transmission no other side effects were observed for a total of 51 procedures. We believe electromagnetically generated shock waves are safe, easy to apply, and relatively effective in the therapy of common bileduct and intrahepatic stones. Images Figure 2 Figure 3 PMID:2311983

While in vitro liver tissue engineering has been increasingly studied during the last several years, presently engineered liver tissues lack the bileduct system. The lack of bile drainage not only hinders essential digestive functions of the liver, but also leads to accumulation of bile that is toxic to hepatocytes and known to cause liver cirrhosis. Clearly, generation of bileduct tissue is essential for engineering functional and healthy liver. Differentiation of human induced pluripotent stem cells (iPSCs) to bileduct tissue requires long and/or complex culture conditions, and has been inefficient so far. Towards generating a fully functional liver containing biliary system, we have developed defined and controlled conditions for efficient 2D and 3D bileduct epithelial tissue generation. A marker for multipotent liver progenitor in both adult human liver and ductal plate in human fetal liver, EpCAM, is highly expressed in hepatic spheroids generated from human iPSCs. The EpCAM high hepatic spheroids can, not only efficiently generate a monolayer of biliary epithelial cells (cholangiocytes), in a 2D differentiation condition, but also form functional ductal structures in a 3D condition. Importantly, this EpCAM high spheroid based biliary tissue generation is significantly faster than other existing methods and does not require cell sorting. In addition, we show that a knock-in CK7 reporter human iPSC line generated by CRISPR/Cas9 genome editing technology greatly facilitates the analysis of biliary differentiation. This new ductal differentiation method will provide a more efficient method of obtaining bileduct cells and tissues, which may facilitate engineering of complete and functional liver tissue in the future. PMID:27138846

Liver fibrosis is a consequence of chronic liver disorders which lead to the accumulation of extracellular matrix (ECM). Particularly, there is an increased accumulation of collagen in the fibrotic liver. We have therefore used a triplex forming oligonucleotide (TFO) against the type α 1 (I) collagen and evaluated, whether it can attenuate liver fibrosis induced by common bileduct ligation (CBDL) in rats. There was a significant decrease in hydroxyproline levels and Masson’s trichrome staining for collagen in TFO-treated CBDL groups compared to non-treated CBDL group. There was over expression of type α1(I) collagen, α-smooth muscle actin (α-SMA) and TGF-β1 expression in the CBDL group compared to TFO-treated CBDL group. Also, the serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were less in the TFO treated group compared to non-treated CBDL group. There was also less neutrophils accumulation in TFO treated CBDL group assayed by myeloperoxidase (MPO) assay. These results suggests that TFO can be used to downregulate type 1 collagen gene expression and can alleviate liver fibrosis induced by common bileduct ligation. PMID:20816672

We report here the first two cases of hepatobiliary pathology in HIV-positive men following recreational use of ketamine: >1 g/day over a 12-month period while on ritonavir-based antiretroviral therapy. Presentation in each case was acute with nausea, vomiting and epigastric pain. Alanine aminotransferase was raised at 3.2× and 10.1 × upper limit of normal and alkaline phosphatase was raised at 1.7× and 2.5 × ULN for cases 1 and 2, respectively. Magnetic resonance cholangiopancreatography showed dilatation of the common bileduct; case 1, 18 mm and case 2, 14 mm with no ductal obstruction on endoscopic retrograde cholangiopancreatography. The symptoms resolved, common bileduct dilatation and liver function improved on discontinuation of ketamine use. Time to development of symptoms is shorter than reported in HIV-negative cases (12 months vs. 4 years) which may be explained by an interaction between ketamine and ritonavir. PMID:23970577

Mucinous cystic neoplasm of the liver (MCN-L) is a very rare tumor whose detailed behavior is still unknown. We describe two cases of MCN-L that exhibited extremely interesting growth patterns, and discuss the characteristics of MCN-Ls. Both cases exhibited MCN-L that originated from the left hepatic lobe (Segment 4) and then prolapsed into the left hepatic duct and common bileduct, resulting in obstructive jaundice due to expansive growth. Endoscopic retrograde cholangiopancreatographies showed the characteristic oval-shaped filling defects in the bileducts. Endoscopic ultrasound and intraductal ultrasound were useful for differentiating the tumors from stones, since multiple septal formations were observed inside the tumors. A literature search revealed that, over the past 10 years, 15 cases of MCN-L (biliary cystadenomas with ovarian-like stroma) that showed expansive growth in the bileduct had been reported. Prolapse into the bileduct and expansive growth appear to be characteristic behavior of MCN-L. In the future, additional data on more cases needs to be collected to further elucidate MCN-L pathophysiology. PMID:25951998

In present study, a novel phospholipid complex loaded cucurbitacin B modified with berberine hydrochloride (CUB-PLC-BER) was prepared by a simple solvent evaporation method with the aim of improving bileduct-targeted drug delivery and therapeutic efficacy for cholangiocarcinoma (CC). The complex's physicochemical properties were systemically investigated in terms of scanning electron microscopy (SEM), x-ray diffraction (XRD) and infrared absorption spectroscopy (IR). In vivo and in vitro antitumor studies, CUB-PLC-BER and the unmodified cucurbitacin B-phospholipid complex (CUB-PLC) presented stronger antitumor efficacy against human cholangiocarcinoma cells (QBC939 cells) than free cucurbitacin B (CUB), while phospholipids (PL) itself had no significant toxicity. Besides that, CUB-PLC showed the advantage over the free CUB and CUB-PLC-BER with regard to the inhibition of tumor growth in vivo antitumor study. Failure to establish the orthotopic CC model, the study attempted to measure the level of CUB in plasma and in bile to explore bileduct-targeted effect indirectly. In the pharmacokinetics study in rats, the average values of Cmax and AUC0-8h of CUB-PLC-BER group in rat bile were higher than those of CUB-PLC, while an opposite result was found in plasma. Meanwhile, the Cmax, AUC0-8h and AUC0-24h of CUB were the least both in plasma and in bile. The results indicated that the CUB-PLC-BER tended to provide a high and prolonged drug concentration to bileduct, and PL played a central role in internalizing CUB into cells to improve the water insoluble drug's permeability, which was of great benefit to enhance the bioavailability of CUB and improve therapeutic efficacy of CC. These results elucidated the potential of CUB-PLC-BER as drug delivery system for improving bileduct-targeted and therapeutic efficacy for CC. PMID:25882012

Distal extrahepatic bileduct (EBD) carcinoma is a rare but highly aggressive malignant neoplasm. Some in vitro studies have shown that EGFR and PI3K-Akt pathway play an important role in the carcinogenesis of bileduct carcinoma. The aim of the present study is to investigate the expression of EGFR, p-AKT, and COX-2 and the mutation of PIK3CA in distal EBD carcinoma and evaluate the association with clinicopathological factors. Ninety cases of distal extrahepatic bileduct (EBD) carcinoma specimens were studied. Immunohistochemistry (IHC) using antibodies against EGFR, p-AKT, and COX-2 was performed on TMA blocks. The PIK3CA mutation was evaluated using the PNAClamp Detection Kit from DNA samples extracted from formalin fixed, paraffin embedded tissue. EGFR expression of distal EBD carcinomas was 61.9%, 26.2%, 6.0% and 6.0% in the negative, weakly positive, moderately positive, and strongly positive groups, respectively. Positive EGFR expression showed significant relationships with high T stage (p = 0.024). In Kaplan-Meier analysis, EGFR expression was associated with shorter cancer-specific overall survival (p = 0.005). Multivariate analysis also showed that moderate or strong (2+ or 3+) EGFR expression was a significant prognostic factor in distal EBD carcinoma: HR 5.286; p = 0.001. Ninety cases of EBD carcinoma tissue were analysed for hotspot mutations (exon 9 and 20) in the PIK3CA gene. Only one mutation was detected: a missense mutation of H1047 at exon 20. The expression levels of p-AKT and COX-2 showed no association with any clinicopathological parameters, including survival rate. Moderate and strong EGFR expressions demonstrate a direct link to poor prognosis. Although further study is warranted to understand the clinicopathological significance, our finding suggests EGFR is a useful prognostic marker of patients with distal EBD carcinoma. A low prevalence of PIK3CA mutation exists in the distal EBD carcinoma of Korean patients, indicating that

In 1970, a Japanese group reported the first use of endoscopic retrograde cholangiopancreatography (ERCP), which is now carried out worldwide. Selective bileduct cannulation is a mandatory technique for diagnostic and therapeutic ERCP. Development of the endoscope and other devices has contributed to the extended use of ERCP, which has become a basic procedure to diagnose and treat pancreaticobiliary diseases. Various techniques related to selective bileduct cannulation have been widely applied. Although the classical contrast medium injection cannulation technique remains valuable, use of wire-guided cannulation has expanded since the early 2000s, and the technique is now widely carried out in the USA and Europe. Endoscopists must pay particular attention to a patient's condition and make an attendant choice about the most effective technique for selective bileduct cannulation. Some techniques have the potential to shorten procedure time and reduce the incidence of adverse events, particularly post-ERCP pancreatitis. However, a great deal of experience is required and endoscopists must be skilled in a variety of techniques. Although the development of the transpapillary biliary cannulation approach is remarkable, it is important to note that, to date, there have been no reports of transpapillary cannulation preventing post-ERCP pancreatitis. In the present article, selective bileduct cannulation techniques in the context of recent Japanese randomized controlled trials and cases of precut sphincterotomy are reviewed and discussed. PMID:26825609

On the eighth day after ligation of the common bileduct in rats a significant increase in the serum content of total lipids, cholesterol bilirubin and ALT, alkaline phosphatase, and gamma-glutamyltransferase was observed. In the microsomal fraction there was a marked decrease in the content and activity of microsomal monooxygenases. Introperitoneal injection of berberine (10 mg/kg) for 6 days caused a partial normalization of permeability of hepatocytes plasma membranes and activity microsomal flavin-containing monooxygenases. It is suggested that berberine is a substrate and inducer of flavin-containing monooxygenases. Membrane-stabilizing effect of berberine is probably realized at the level of inhibition of prooxidant status of liver cells. PMID:23650726

Hyperbilirubinemia (HB) is sometimes encountered following bile-duct cannulation in rats. It possibly originates from the reduced functioning of multidrug resistance-associated protein 2 (Mrp2) and subsequent adaptive alterations in the expression of Mrp3 and the organic anion transporting polypeptides (Oatps). Our aim was to clarify the importance of excluding bile-duct-cannulated (BDC) rats with HB for proper conduct of drug excretion studies. We detected HB [serum total bilirubin concentration (TBIL) ≥0.20 mg/dl] in 16% of all BDC rats prepared. The serum activities of aspartate aminotransferase, alanine aminotransferase, leucine aminopeptidase, and alkaline phosphatase were within the respective normal ranges in the BDC rats with mild HB (TBIL, 0.20-0.79 mg/dl), indicating the absence of hepatic failure. In the pharmacokinetics of pravastatin, an Oatps/Mrp2 probe drug in the BDC rats, the apparent volume of distribution and the clearance were smaller in the mild HB group as compared with the normal group, suggesting the reduction of apparent hepatic uptake and hepatobiliary elimination. The biliary excretion (percentage of dose) was significantly reduced by 54%, suggesting that the biliary efflux activity via Mrp2 was reduced to a greater extent relative to metabolic activity in hepatocytes. The serum γ-glutamyltransferase (GGT) activity correlated with TBIL and inversely correlated with biliary excretion of pravastatin, a finding which could serve as a clue to uncover the regulatory system involving cooperation between GGT and Mrp2. In conclusion, BDC rats with HB, however mild, should be excluded from drug excretion studies to avoid the risk of underestimation of the biliary excretion of drugs. PMID:27208382

Cholestasis-induced liver injury during bileduct obstruction causes an acute inflammatory response. To further characterize the mechanisms underlying the neutrophil-induced cell damage in the bileduct ligation (BDL) model, we performed experiments using wild-type (WT) and ICAM-1-deficient mice. After BDL for 3 days, increased ICAM-1 expression was observed along sinusoids, along portal veins, and on hepatocytes in livers of WT animals. Neutrophils accumulated in sinusoids [358 +/- 44 neutrophils/20 high-power fields (HPF)] and >50% extravasated into the parenchymal tissue. Plasma alanine transaminase (ALT) levels increased by 23-fold, and severe liver cell necrosis (47 +/- 11% of total cells) was observed. Chlorotyrosine-protein adducts (a marker for neutrophil-derived hypochlorous acid) and 4-hydroxynonenal adducts (a lipid peroxidation product) were detected in these livers. Neutrophils also accumulated in the portal venules and extravasated into the portal tracts. However, no evidence for chlorotyrosine or 4-hydroxynonenal protein adducts was detected in portal tracts. ICAM-1-deficient mice showed 67% reduction in plasma ALT levels and 83% reduction in necrosis after BDL compared with WT animals. The total number of neutrophils in the liver was reduced (126 +/- 25/20 HPF), and 85% of these leukocytes remained in sinusoids. Moreover, these livers showed minimal staining for chlorotyrosine and 4-hydroxynonenal adducts, indicating a substantially reduced oxidant stress and a diminished cytokine response. Thus neutrophils relevant for the aggravation of acute cholestatic liver injury in BDL mice accumulate in hepatic sinusoids, extravasate into the tissue dependent on ICAM-1, and cause cell damage involving reactive oxygen formation. PMID:14563671

Postcholecystectomy bileduct injuries (BDI) produce hepatic cholestasis and cause infection of the biliary tract. The biliary cells participate in secreting cytokines and in expression of immune response receptors. Toll-like receptors (TLRs) conduct signalling and activate the innate and adaptive inflammatory response. The objective was to determine the serum levels of TLR-2 and the expression of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients. A transverse, analytical study with 2 groups was done. One group included healthy volunteers (control group) and other included 25 postcholecystectomy BDI patients with complete biliary obstruction. Using the Enzyme-linked Immunosorbent Assay (ELISA) technique, serum levels of TLR-2 were determined, and with immunofluorescence the morphologic analysis of TLR-1 and TLR-2 and β-defensin in liver biopsies of postcholecystectomy BDI patients was performed. The average TLR-2 serum level in the control group was 0.0 pg/mL and in the BDI group, 0.023 ± 0.0045 pg/mL (P < 0.0001, bilateral Mann Whitney U). Immunofluorescence was used to determine the expression in liver biopsies, blood vessels, bileducts, and hepatic parenchyma where 12 hepatic biopsies were positive for TLR-1 with average of 3213057.74 ± 1071019.25 μm2; and 7 biopsies were positive for β-defensin with an average of 730364.33 ± 210838.02 μm2; and 6 biopsies positive for TLR-2, obtaining an average of 3354364.24 ± 838591.06 μm2. In conclusion, TLR-1 and TLR-2 and β-defensin play an important role in the innate antimicrobial defense of the hepatobiliary system. PMID:25755667

Cystadenomas of the liver and extrahepatic bileducts (EHBD) are uncommon but distinctive neoplasms whose terminology and epithelial phenotype have been a source of controversy. We reviewed 20 cases, 16 arising in the liver and 4 in the EHBD. Eighteen patients were women, with a mean age of 36.5 years. Eighteen tumors were multiloculated and 2 were unilocular. The tumor size ranged from 4 to 29 cm (average, 11 cm). The cyst fluid in 13 tumors was described as serous, in 2 as clear, in 2 others as hemorrhagic, and in 1 as serous and mucinous. Only in 2 tumors was the fluid described as mucinous. In 18 cystadenomas, the predominant epithelial lining consisted of a single layer of cuboidal or low-columnar nondysplastic cells similar to those of the gallbladder or bileducts. This epithelial lining was strongly positive for cytokeratins 7 and 19, and focally positive for MUC1. Only 2 cystadenomas showed predominant intestinal differentiation characterized by mature goblet cells and columnar absorptive cells. These cells expressed CDX2, MUC2, and cytokeratin 20. Admixed with the goblet and columnar cells, there were serotonin-containing cells and Paneth cells. These 2 tumors showed extensive areas of high-grade dysplasia and invasive adenocarcinoma with intestinal phenotype. A subepithelial ovarian-like stroma was present in all tumors. None of the patients died of the tumors. We believe that the term mucinous cystic tumor recommended by the World Health Organization for all cystadenomas of the liver and EHBD is a misnomer. PMID:25792461

A comparative topography and morphometry of the common bileduct and major duodenal papilla was studied on the extrahepatic biliary apparatus of human and major domesticated animals such as horse, ox, Black Bengal (BB) goat, sheep, dog and cat of local breed. In Black Bengal goat, sheep, dog and cat, the extrahepatic biliary system seemed to be the continuation of the cystic duct, which was found to continue as the common hepatic/common bileduct into which all the hepatic/lobar ducts open. In man, the mean length and the mean diameter of the common bileduct were 7.67+/-0.58 cm. and 7.27+/-0.77 mm. respectively. In the ox, these values were 1.57+/-0.72 cm. and 11.82+/-0.79 mm. respectively; in the Black Bengal goat, 7.23+/-0.74 cm. and 4.45+/-0.72 mm. respectively; in the sheep, 5.27+/-0.66 cm. and 3.75+/-0.79 mm. respectively; in the dog, 4.72+/-0.67 cm. and 6.43+/-0.55 mm. respectively and in the cat, 3.26+/-0.87 cm. and 5.63+/-0.43 mm. respectively. In man, the mean length and the mean diameter at the base of the MDP were 4.37+/-0.56 mm. and 3.97+/-0.72 mm. respectively. In horse, these were 52.36+/-0.67 mm. and 12.47+/-0.63 mm. respectively; in ox, 12.53+/-0.73 mm. and 8.83+/-0.68 mm. respectively; in Black Bengal goat, 14.36+/-0.55 mm. and 5.23+/-0.57 mm. respectively; in sheep, 11.27+/-0.69 mm. and 4.51+/-0.74 mm. respectively; in dog, 17.43+/-0.82 mm. and 6.72+/-0.64 mm. respectively and in cat, these values were 12.36+/-0.47 mm. and 7.12+/-0.87 mm. The distance of the Major Duodenal Papilla (MDP) form the pyloric end of the stomach was proportionately shorter in the meat-eaters, i.e., the omnivorous man (9.76+/-0.88 cm), and the carnivores, dog (6.37+/-0.73 cm) and cat (2.75+/-0.87 cm.) when compared to that of the herbivores, i.e., ox (55.37+/-0.68 cm.), BB goat (23.27+/-0.89 cm.) and sheep (25.62+/-0.77 cm.). In the horse, the major duodenal papilla was perpendicular to the duodenal mucosal surface with the largest mean length and the mean diameter. In

Laparoscopic cholecystectomy (LC) has been recently adapted to acute cholecystitis. Major bileduct injury during LC, especially Strasberg-Bismuth classification type E, can be a critical problem sometimes requiring hepatectomy. Safety and definitive treatment without further morbidities, such as posthepatectomy liver failure, is required. Here, we report a case of severe bileduct injury treated with a stepwise approach using (99m)Tc-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging to accurately estimate liver function.A 52-year-old woman diagnosed with acute cholecystitis underwent LC at another hospital and was transferred to our university hospital for persistent bile leakage on postoperative day 20. She had no jaundice or infection, although an intraperitoneal drainage tube discharged approximately 500 ml of bile per day. Recorded operation procedure showed removal of the gallbladder with a part of the common bileduct due to its misidentification, and each of the hepatic ducts and right hepatic artery was injured. Abdominal enhanced CT revealed obstructive jaundice of the left liver and arterial shunt through the hilar plate to the right liver. Magnetic resonance cholangiopancreatography revealed type E4 or more advanced bileduct injury according to the Bismuth-Strasberg classification. We planned a stepwise approach using percutaneous transhepatic cholangiodrainage (PTCD) and portal vein embolization (PVE) for secure right hemihepatectomy and biliary-jejunum reconstruction and employed (99m)Tc-GSA SPECT/CT fusion imaging to estimate future remnant liver function. The left liver function rate had changed from 26.2 % on admission to 26.3 % after PTCD and 54.5 % after PVE, while the left liver volume rate was 33.8, 33.3, and 49.6 %, respectively. The increase of liver function was higher than that of volume (28.3 vs. 15.8 %). On postoperative day 63, the curative operation, right

Biliary distomatosis is caused by a parasitis of trematode family: the fascialo hepatica. It is a rare affection in Tunisia. The diagnostic is often done in the status phase. Adult parasite stay preferentially at biliary ducts, cause obstruction and cholangitis. The authors report a case of biliary treated successfully by laparoscopic procedure. PMID:17042216

The sphincter of Oddi (SO) regulates trans-sphincteric flow (TSF) by acting primarily as a pump or as a resistor in specific species. We used the Australian possum SO, which functions similarly to the human SO, to characterize SO motility responses to different common bileduct (CBD) and duodenal pressures. Possum CBD, SO and attached duodenum (n = 18) was mounted in an organ bath. External reservoirs were used to impose CBD (0–17 mmHg) and duodenal (0, 4, 7 mmHg) pressure. Spontaneous SO activity was recorded using four-lumen pico-manometry and TSF was measured gravimetrically. Temporal analysis of manometric and TSF recordings identified three functionally distinct biliary-SO regions, the proximal-SO (juxta-CBD), body-SO and papilla-SO. At CBD pressures < 3 mmHg the motor activity of these regions was coordinated to pump fluid. Proximal-SO contractions isolated fluid within the body-SO. Peristaltic contraction through the body-SO pumped this fluid through the papilla-SO (17–27 μl contraction), which opened to facilitate flow. CBD pressure > 3.5 mmHg resulted in progressive changes in TSF to predominantly passive ‘resistor’-type flow, occurring during proximal-SO–body-SO quiescence, when CBD pressure exceeded the pressure at the papilla-SO. Progression from pump to resistor function commenced when CBD pressure was 2–4 mmHg greater than duodenal pressure. These results imply that TSF is dependent on the CBD–duodenal pressure difference. The papilla-SO is pivotal to TSF, relaxing during proximal-SO–body-SO pumping and closing during proximal-SO–body-SO quiescence. The pump function promotes TSF at low CBD pressure and prevents bile stasis. At higher CBD pressure, the papilla-SO permits TSF along a pressure gradient, thereby maintaining a low pressure within the biliary tract. PMID:15169843

It has been observed that polymorphonuclear neutrophils (PMN) increase in number and function during obstructive jaundice (OJ). However, the precise mechanisms underlying PMN apoptosis during OJ remain poorly understood. The aim of the present study was to investigate the modulation of cytochrome c (Cytc) on the mitochondrial signaling pathway in bileduct-ligated (BDL) rats and the effect on PMN apoptosis following the intravenous administration of Cytc. Rats were randomly divided into four groups: A control group, a sham group, a BDL group and a BDL + Cytc group (rats with common bileduct ligation as well as Cytc intravenous injection). Blood samples were collected from the inferior vein cava for biochemical analysis and separation of the PMN. PMN apoptosis was evaluated using flow cytometry. The mitochondrial membrane potential (ΔΨm) of PMN was detected by rhodamine-123 staining. The Cytc protein expression levels were examined using western blotting. PMN mitochondria were observed using transmission electron microscopy. The results of the present study revealed that the PMN apoptosis rate in rats decreased gradually from 12 to 72 h following BDL to levels that were significantly lower than those of the control group and the sham group. Compared with the corresponding time point of the BDL group, the BDL + Cytc group showed a significantly increased PMN apoptosis rate. The mean fluorescence intensity (MFI) of ΔΨm decreased from 12 to 72 h following BDL, and was significantly increased compared with the control and sham groups. MFI in the BDL + Cytc group was higher compared with that in the BDL group. Cytc expression levels increased in the mitochondria and decreased in the cytoplasm from the 12 to 72 h in the BDL group, which was significantly different from that in the control and sham groups at the corresponding time points. Compared with the BDL group, Cytc expression levels in the cytoplasm for the BDL + Cytc group tended to gradually and significantly

AIM: To investigate the safety and feasibility of needlescopic grasper-assisted single-incision laparoscopic common bileduct exploration (nSIL-CBDE) by comparing the surgical outcomes of this technique with those of conventional laparoscopic CBDE (CL-CBDE). METHODS: We retrospectively analyzed the clinical data of patients who underwent CL-CBDE or nSIL-CBDE for the treatment of common bileduct (CBD) stones between January 2000 and December 2014. For performing nSIL-CBDE, a needlescopic grasper was also inserted through a direct puncture below the right subcostal line after introducing a single-port through the umbilicus. The needlescopic grasper helped obtain the critical view of safety by retracting the gallbladder laterally and by preventing crossing or conflict between laparoscopic instruments. The gallbladder was then partially dissected from the liver bed and used for retraction. CBD stones were usually extracted through a longitudinal supraduodenal choledochotomy, mostly using ﬂushing a copious amount of normal saline through a ureteral catheter. Afterward, for the certification of CBD clearance, CBDE was performed mostly using a ﬂexible choledochoscope. The choledochotomy site was primarily closed without using a T-tube, and simultaneous cholecystectomies were performed. RESULTS: During the study period, 40 patients underwent laparoscopic CBDE. Of these patients, 20 underwent CL-CBDE and 20 underwent nSIL-CBDE. The operative time for nSIL-CBDE was significantly longer than that for CL-CBDE (238 ± 76 min vs 192 ± 39 min, P = 0.007). The stone clearance rate was 100% (40/40) in both groups. Postoperatively, the nSIL-CBDE group required less intravenous analgesic (pethidine) (46.5 ± 63.5 mg/kg vs 92.5 ± 120.1 mg/kg, P = 0.010) and had a shorter hospital stay than the CL-CBDE group (3.8 ± 2.0 d vs 5.1 ± 1.7 d, P = 0.010). There was no significant difference in the incidence of postoperative complications between the two groups. CONCLUSION: The

Following transrectal administration, {sup 123}I iodoamphetamine (IMP) has been shown in both animal and patient studies to be capable of detecting the presence of portasystemic shunting (PSS). However, the ability of this method to actually quantitate PSS in the presence of cirrhosis and propranolol has not been demonstrated. We studied nine dogs with hitologically proven cirrhosis induced by chronic bileduct ligation. After intravenous injection of propranolol, PSS were measured with both the IMP method and the standard of portal vein infusion of {sup 99m}Tc macroaggregated albumin (MAA) given through a mesenteric vein catheter. Based on linear regression, a close relationship was seen, given by the equation: MAA = IMP 0.9 + 0.035, with correlation coefficient of 0.99. Thus, in dogs with cirrhosis secondary to chronic bileduct ligation and after propranolol administration, PSS can be quantitated with the transrectal IMP method.

Interferons are known to prevent liver collagen by an antifibrogenic mechanism that involves mRNA procollagen regulation. The aim of the present work was to determine whether interferon could also decrease collagen by increasing its degradation. Fibrosis was induced in male Wistar rats by double ligation and section of the common bileduct. Interferon-alpha 2b (100,000 IU/rat s.c.) was administered to bileduct ligated rats daily after surgery for 4 weeks. Interferon increased the capacity of the liver to degrade type I and III collagens and matrigel. In addition, the plasminogen activator activity also increased. Since plasminogens are thought to be key participants in the balance of proteolytic activities that regulate extracellular matrix degradation, their elevation may also provide another antifibrotic (proteolytic) mechanism of action of interferon. PMID:8966190

Carcinoid tumours of the common bileduct represent an extremely rare entity. Similarly, primary follicular lymphomas of the ampulla of Vater constitute an infrequent neoplasia. Herein, we report the first case of a synchronous development of a carcinoid tumour of the common bileduct and an ampullary follicular lymphoma that was treated surgically with a Whipple's procedure, due to inability to establish definitive preoperative diagnosis despite the extensive diagnostic investigation. PMID:21232154

A survey of Victorian surgeons performing laparoscopic cholecystectomy was carried out. This report discusses the bileduct injuries identified in the survey. Twelve injuries were recorded, a rate of 0.2%. Three of the 12 required formal repair, the other 9 being treated by T-tube alone. Possible mechanisms of these injuries, the experience of the surgeon, the role of operative cholangiography and delays in recognition of the injury are discussed. PMID:8363476

Polycystic kidney (PCK) rats, an animal model of Caroli's disease, show a dilatation of intrahepatic bileducts (IHBD) called "ductal plate malformation." Mesenchymal cells and the Notch and Hedgehog signaling pathways in portal tracts are reportedly involved in the normal development of IHBD, although there have been no studies on the roles of these signaling pathways in PCK rats. We immunohistochemically examined the expression of the molecules related to these signaling pathways in portal tracts. All molecules related to these signaling pathways expressed in portal tracts in Sprague Dawley (SD) rats (control) were also expressed in PCK rats. Mesenchymal cells (myofibroblasts) were frequently found in the connective tissue of portal tracts of 20 embryonic-day-old (E20D), 1-day-old (1D), and 1-week-old (1W) SD and PCK rats and were abundant in PCK rats. Interestingly, myofibroblasts almost disappeared at in both strains of 3W rats. Jagged1 was expressed in mesenchymal cells in portal tracts and was abundant in PCK rats. Double immunostaining showed that Jagged1-positive cells were myofibroblasts. Notch2 and HES1 were expressed in cholangiocytes of the bileducts of both rats. Sonic Hedgehog was similarly expressed in the bileducts of both rats. A well-balanced and time-sequential expression of the Notch and Hedgehog family in portal tracts might be essential for the normal development of IHBD in E20D to 1W SD rats, and an imbalanced interaction of these molecules, particularly increased Jagged1 expression in periductal and periportal myofibroblasts and Notch2 expressed in cholangiocytes, may be involved in the formation of bileduct lesions in PCK rats. PMID:23331119

Liver transplantation and cholangiocarcinoma induce biliary dysfunction following ischemia reperfusion (IR). The function of the intrahepatic biliary tree is regulated by both autocrine and paracrine factors. The aim of the study was to demonstrate that IR-induced damage of cholangiocytes is associated with altered expression of biliary angiogenic factors. Normal and bileduct ligation rats underwent 24-h sham or hepatic reperfusion after 30 min of transient occlusion of the hepatic artery (HAIR) or portal vein (PVIR) before collecting liver blocks and cholangiocyte RNA or protein. We evaluated liver histology, biliary apoptosis, proliferation and expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2 in liver sections and isolated small and large cholangiocytes. Normal rat intrahepatic cholangiocyte cultures (NRICC) were maintained under standard conditions in normoxic or under a hypoxic atmosphere for 4 h and then transferred to normal conditions for selected times. Subsequently, we measured changes in biliary proliferation and apoptosis and the expression of VEGF-A/C and VEGFR-2/3. In vivo, HAIR (but not PVIR) induced damage of large bileducts and decreased proliferation and secretin-stimulated cAMP levels. HAIR-induced damage of large bileducts was associated with increased expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2. In vitro, under hypoxic conditions, there was increased apoptosis and reduced proliferation of NRICC concomitant with enhanced expression of VEGF-A/C and VEGFR-2/3. The functional damage of large bileducts by HAIR and hypoxia is associated with increased expression of angiogenic factors in small cholangiocytes, presumably due to a compensatory mechanism in response to biliary damage. PMID:26451003

Obstructive cholestasis is characterized by impairment of hepatic canalicular bile efflux and there are no clinically effective drugs to cure except surgeries. Previously we revealed that oleanolic acid (OA) protected against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice. Cholestasis caused by LCA is characterized by segmental bileduct obstruction, whether OA possesses the beneficial effect on completed obstructive cholestasis induced by bileduct ligation (BDL) remains unknown. In this study, we demonstrated that BDL-induced mice liver pathological change, and increase in serum levels of ALT, AST and ALP were all significantly reduced by OA (20 mg/kg, i.p.). Meanwhile, OA also lowered total bilirubin and total bile acids levels in serum, as well as total bile acids level in liver, in contrast, urinary total bile acids output was remarkably up-regulated by OA. Gene expression analysis showed that OA caused significant increased mRNA expression of MRP3 and MRP4 located at hepatic basolateral membrane, and restoration of MRP2 and BSEP located at hepatic cannalicular membrane. Furthermore, significant NRF2 protein accumulation in nucleus was also observed in OA treated mice. In mice primary cultured hepatocytes, the effects of OA on MRP2, MRP3 and MRP4 expression were directly proved to be mediated via NRF2 activation, and BSEP downregulation induced by OA was in part due to FXR antagonism. Luciferase assay performed in Hep G2 cells also illustrated that OA was a partial FXR antagonist. Taken together, we conclude that OA attenuates obstructive cholestasis in BDL mice, possibly via activation of NRF2-MRPs and FXR antagonism. PMID:26297978

ABSTRACT Background: Once a biliary injury has occurred, repair is done by a hepaticojejunostomy. The most common procedure is to perform a dilatation with balloon with a success of 70 %. Success rates range using biodegradable stents is from 85% to 95%. Biodegradable biliary stents should change the treatment of this complication. Aim: To investigate the use of biodegradable stents in a group of patients with hepaticojejunonostomy strictures. Methods: In a prospective study 16 biodegradable stents were placed in 13 patients with hepaticojejunostomy strictures secondary to bileduct repair of a biliary surgical injury. Average age was 38.7 years (23-67), nine were female and four male. All cases had a percutaneous drainage before at the time of biodegradable stent placement. Results: In one case, temporary haemobilia was present requiring blood transfusion. In another, pain after stent placement required intravenous medication. In the other 11 patients, hospital discharge was the next morning following stent placement. During the patient´s follow-up, none presented symptoms during the first nine months. One patient presented significant alkaline phosphatase elevation and stricture recurrence was confirmed. One case had recurrence of cholangitis 11 months after the stent placement. 84.6% continued asymptomatic with a mean follow-up of 20 months. Conclusion: The placement of biodegradable stents is a safe and feasible technique. Was not observed strictures caused by the stent or its degradation. It could substitute balloon dilation in strictures of hepaticojejunostomy. PMID:27438039

With the advent of minimal access biliary procedures there is a need for a safe intracorporal lithotripsy technique that can be used through small flexible endoscopes. Currently, the two techniques available are electrohydraulic lithotripsy and laser induced shock wave lithotripsy. In this study we compare the effect of a 504 nm coumarin pulsed dye laser and electrohydraulic lithotripsy on in vitro porcine gallbladder and common bileduct. Electrohydraulic lithotripsy at the lowest energy the generator would deliver caused perforation of both tissues in only a few pulses when a 1.9-F probe was placed in direct contact with the tissue. Energy from a 504 nm coumarin pulsed dye laser delivered through a 320-microns fiber placed in light contact with the tissue caused an energy-dependent perforation after 50 pulses in from none to 44% of tissues. It was also found that there was a higher incidence of perforation in more vascular than non-vascular tissue. When the EHL probe and the laser fiber were held 1-2 mm from the tissue surface, discharge of each resulted in no perforation. On histological examination of the tissues, the perforations were found to be very small with laser lithotripsy and considerably larger with the electrohydraulic lithotripsy. It was felt that laser lithotripsy in the clinical situation was likely to be much safer than electrohydraulic lithotripsy. PMID:1349415

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. However, the pathomechanisms of the disease remains obscure. Neuropathological studies have demonstrated a primary gliopathy in humans as well as in animal models of chronic and acute liver failure. Here, we have investigated in an animal model of mild HE: the bileduct ligated rat (BDL) at the cirrhotic stage (4 weeks after surgery), the expression of the key marker of mature astrocytes; the glial fibrillary acidic protein (GFAP) in different brain areas such as: Substantia nigra pars compacta (SNc), Ventral tegmental area (VTA), hippocampus, dorsal striatum and brain cortex by means of immunohistochemistry. The immunohistochemical study showed, in BDL compared to the operated controls (shams), a diminished astrocyte reactivity corresponding to a loss of GFAP expression within SNc, VTA, hippocampus and dorsal striatum (p<0.05),whereas in the brain cortex astrocytes appeared strongly immunoreactive with increased GFAP expression (p<0.05) as compared to shams. Our finding demonstrated differential astroglial responses which depend to the specificity of the area investigated and its particular neuronal neighboring environment, and could have possible outcomes on the diverse neuronal functions especially those observed during the different episodes of hepatic encephalopathy. PMID:26995310

OBJECTIVE: The authors determined the most useful predictors of common bileduct (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent laparoscopic cholecystectomy (LC). METHODS: Prospective and retrospective collection of historical, biochemical and ultrasonographic data was used. Receiver operating characteristics curve analysis was used to determine optimal biochemical cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones also was employed. Prospective validation of the model was performed on an independent group of patients. RESULTS: Endoscopic retrograde cholangiopancreatographies were performed before LC in 106 patients, and after LC in 33. Only four of ten clinical variables evaluated independently predicted the presence of CBD stones. The optimal model predicted a 94% probability of CBD stones in a patient older than 55 years of age who presented with an elevated bilirubin (over 30 mumol/L) and positive ultrasound findings (a dilated CBD, and a CBD stone seen on ultrasound). This model was validated prospectively in a subsequent series of 49 patients in which the probability of CBD stone was only 8% when all four predictors were absent. CONCLUSIONS: The identified independent clinical predictors of a CBD stone helps select a population of symptomatic gallstone bearers who benefit most from cholangiographic assessment. PMID:7517657

Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bileduct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

Intraductal papillary neoplasms of the bileduct (IPNB) leads to malignant transformation and mucin production. Herein, we presented two cases of mucin-producing IPNB with obstructive jaundice who underwent resection of the intrahepatic lesions and bypass hepaticojejunostomy. The first case was a 69 year-old male patient with 5-year follow up for gallstone disease. Imaging studies showed mucin-secreting IPNB mainly in the hepatic segment III bileduct (B3) and multiple intrahepatic duct stones for which, segment III resection, intrahepatic stone removal, end-to-side choledochojejunostomy and B3 hepaticojejunostomy were conducted. The second case was a 74 year-old female patient with 11-year follow up for gallstone disease. Imaging studies showed mucin-producing IPNB with dilatation of the segment IV duct (B4) and mural nodules for which, segment IV resection, partial resection of the diaphragm and central hepaticojejunostomy were conducted. Both patients recovered uneventfully from surgery. These cases highlight that in patients with IPNB, abundant production of highly viscous mucin inducing obstructive jaundice may be associated with malignant transformation. PMID:27621752

Anti-inflammatory and antifibrotic effects of the broad spectrum phosphodiesterase (PDE) inhibitor pentoxifylline have suggested an important role for cyclic nucleotides in the pathogenesis of hepatic fibrosis; however, studies examining the role of specific PDEs are lacking. Endotoxemia and Toll-like receptor 4 (TLR4)-mediated inflammatory and profibrotic signaling play a major role in the development of hepatic fibrosis. Because cAMP-specific PDE4 critically regulates lipopolysaccharide (LPS)-TLR4-induced inflammatory cytokine expression, its pathogenic role in bileduct ligation-induced hepatic injury and fibrogenesis in Sprague-Dawley rats was examined. Initiation of cholestatic liver injury and fibrosis was accompanied by a significant induction of PDE4A, B, and D expression and activity. Treatment with the PDE4-specific inhibitor rolipram significantly decreased liver PDE4 activity, hepatic inflammatory and profibrotic cytokine expression, injury, and fibrosis. At the cellular level, in relevance to endotoxemia and inflammatory cytokine production, PDE4B was observed to play a major regulatory role in the LPS-inducible tumor necrosis factor (TNF) production by isolated Kupffer cells. Moreover, PDE4 expression was also involved in the in vitro activation and transdifferentiation of isolated hepatic stellate cells (HSCs). Particularly, PDE4A, B, and D upregulation preceded induction of the HSC activation marker α-smooth muscle actin (α-SMA). In vitro treatment of HSCs with rolipram effectively attenuated α-SMA, collagen expression, and accompanying morphologic changes. Overall, these data strongly suggest that upregulation of PDE4 expression during cholestatic liver injury plays a potential pathogenic role in the development of inflammation, injury, and fibrosis. PMID:23887098

Introduction During laparoscopic cholecystectomy, intraoperative cholangiography (IOC) is currently regarded as the gold standard in the detection of choledocholithiasis. Laparoscopic ultrasonography (LUS) is an attractive alternative with several potential advantages. Methods A systematic review was undertaken of the published literature comparing LUS with IOC in the assessment of common bileduct (CBD) stones. Results Twenty-one comparative studies were analysed. There were 4,566 patients in the IOC group and 5,044 in the LUS group. The combined sensitivity and specificity of IOC in the detection of CBD stones were 0.87 (95% confidence interval [CI]: 0.83-0.89) and 0.98 (95% CI: 0.98-0.98) respectively with a pooled area under the curve (AUC) of 0.985 and a diagnostic odds ratio (OR) of 260.65 (95% CI: 160.44-423.45). This compares with a sensitivity and specificity for LUS of 0.90 (95% CI: 0.87-0.92) and 0.99 (95% CI: 0.99-0.99) respectively with a pooled AUC of 0.982 and a diagnostic OR of 765.15 (95% CI: 450.78-1,298.76). LUS appeared to be more successful in terms of coming to a clinical decision regarding CBD stones than IOC (random effects, risk ratio: 0.95, 95% CI: 0.93-0.98, df=20, z=-3.7, p<0.005). Furthermore, LUS took less time (random effects, standardised mean difference: 0.95, 95% CI: 0.93-0.98, df=20, z=-3.7, p<0.005). Conclusions LUS is comparable with IOC in the detection of CBD stones. The main advantages of LUS are that it does not involve ionising radiation, is quicker to perform, has a lower failure rate and can be repeated during the procedure as required. PMID:26985813

Cytosolic Ca2+ (Cai2+) regulates secretion of bicarbonate and other ions in the cholangiocyte. In other cell types, this second messenger acts through Ca2+ waves, Ca2+ oscillations, and other subcellular Ca2+ signaling patterns, but little is known about the subcellular organization of Ca2+ signaling in cholangiocytes. Therefore, we examined Ca2+ signaling and the subcellular distribution of Ca2+ release channels in cholangiocytes and in a model cholangiocyte cell line. The expression and subcellular distribution of inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) isoforms and the ryanodine receptor (RyR) were determined in cholangiocytes from normal rat liver and in the normal rat cholangiocyte (NRC) polarized bileduct cell line. Subcellular Ca2+ signaling in cholangiocytes was examined by confocal microscopy. All 3 InsP3R isoforms were expressed in cholangiocytes, whereas RyR was not expressed. The type III InsP3R was the most heavily expressed isoform at the protein level and was concentrated apically, whereas the type I and type II isoforms were expressed more uniformly. The type III InsP3R was expressed even more heavily in NRC cells but was concentrated apically in these cells as well. Adenosine triphosphate (ATP), which increases Ca2+ via InsP3 in cholangiocytes, induced Ca2+ oscillations in both cholangiocytes and NRC cells. Acetylcholine (ACh) induced apical-to-basal Ca2+ waves. In conclusion, Ca2+ signaling in cholangiocytes occurs as polarized Ca2+ waves that begin in the region of the type III InsP3R. Differential subcellular localization of InsP3R isoforms may be an important molecular mechanism for the formation of Ca2+ waves and oscillations in cholangiocytes. Because Cai2+ is in part responsible for regulating ductular secretion, these findings also may have implications for the molecular basis of cholestatic disorders. PMID:12143036

Neutrophils aggravate cholestatic liver injury after bileduct ligation (BDL). Recently, it was suggested that hepatocellular apoptosis might be critical for liver injury in this model. To test the hypothesis that apoptosis could be a signal for neutrophil extravasation and injury, we assessed parameters of apoptosis and inflammation after BDL using 2 different approaches: (1) wild-type and Fas receptor-deficient lpr mice of the C57BL/6J or C3H/HeJ strains, and (2) treatment with the pancaspase inhibitor z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk)in C3HeB/FeJ mice. After BDL for 3 days, total cell death was estimated to be between 10% and 50% of all cells evaluated. However, less than 0.1% of hepatocytes showed apoptotic morphology in all 3 strains. Processing of procaspase-3, caspase-3 enzyme activities, and immunohistochemical staining for cytokeratin 18 cleavage products indicated no activation of caspases. Real-time reverse-transcriptase polymerase chain reaction analysis revealed increased expression of many inflammatory mediators but no effect on proapoptotic genes. More than 50% of all accumulated neutrophils were extravasated and colocalized with foci of oncotic hepatocytes and chlorotyrosine adducts. z-VAD-fmk treatment had no effect on apoptosis or liver injury after BDL but eliminated apoptosis after galactosamine/endotoxin in C3HeB/FeJ mice. In Fas receptor-deficient lpr mice (C57BL/6J), expression of inflammatory mediators, neutrophil accumulation and extravasation, chlorotyrosine adduct formation, and liver injury were reduced. This protection was not observed in lpr mice of the endotoxin-resistant C3H/HeJ strain. In conclusion, liver injury (oncotic necrosis) after BDL correlated with the severity of the inflammatory response. The minimal amount of apoptosis had no effect on inflammation or on the overall injury. PMID:15382126

OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bileduct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA: Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS: Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients. PMID:9923803

The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum (BC703) on bileduct ligation (BDL)-induced hepatic fibrosis in rats. BDL rats were divided into three groups, which orally received distilled water or BC703 (10 or 50 mg/kg/day) for consecutive 28 days. Antifibrotic effects of BC703 on BDL-induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN), transforming growth factor-beta 1 (TGF-β1) and hepatic levels of malondialdehyde (MDA), glutathione (GSH), total superoxide dismutase (SOD) and nitric oxide (NO). The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson's trichrome stain. ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham-operated group. These elevations were significantly decreased by BC703 treatment. Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group. In addition, increases in hepatic MDA and NO levels in the BDL-induced cholestasis were attenuated by BC703 treatment. Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF-β1. Histopathological studies further substantiated the protective effect of BC703 on BDL-induced hepatic fibrosis in rat. BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease. PMID:23424213

A 75-year-old woman with hypertension presented with acute suppurative cholangitis. Chest radiography revealed severe kyphosis. Abdominal computed tomography revealed a large stone impacted in the common bileduct (CBD). The patient underwent emergent endoscopic retrograde cholangiopancreatography, and cholangiography revealed a large stone (7×3 cm) in the CBD that could not be captured using a large basket. We could not use the percutaneous approach for stone fragmentation by using a cholangioscope because of severe degenerative kyphosis. Finally, we performed holmium laser lithotripsy under peroral cholangioscopy by using an ultraslim endoscope, and the large stone in the CBD was successfully fragmented and removed without complications. PMID:27000425

A 75-year-old woman with hypertension presented with acute suppurative cholangitis. Chest radiography revealed severe kyphosis. Abdominal computed tomography revealed a large stone impacted in the common bileduct (CBD). The patient underwent emergent endoscopic retrograde cholangiopancreatography, and cholangiography revealed a large stone (7×3 cm) in the CBD that could not be captured using a large basket. We could not use the percutaneous approach for stone fragmentation by using a cholangioscope because of severe degenerative kyphosis. Finally, we performed holmium laser lithotripsy under peroral cholangioscopy by using an ultraslim endoscope, and the large stone in the CBD was successfully fragmented and removed without complications. PMID:27000425

Public health and financial aspects of cholecystectomy related bileduct injury (BDI) are highlighted in a National Cholecystectomy Survey carried out through 'datamining' the Federal State Medical Records Summaries and Financial Summaries of all Belgian hospitals in 1997. All cancer diagnoses, children < or = 10 years, cholecystectomies performed as an abdominal co-procedure or patients having undergone other non-related surgery were excluded from the study. 10.595 laparoscopic (LC) and 1.033 open cholecystectomies (OC) as well as 137 secondary BDI treatments (LC/OC) were included in the survey (total 11.765). Both LC and OC groups turned out to be significantly different as to distribution of patient's age and APR-DRG severity classes. Composite criteria in terms of ICD-9-CM and billing codes were elaborated to classify: 1) primary, intra-operatively detected and treated BDI (N = 30), 2) primary delayed BDI treatments (N = 38), 3) secondary BDI treatments (N = 137), 4) non-BDI abdomino-surgical complications (N = 119), 4) uneventful laparoscopic (N = 7.476) and 5) uneventful open cholecystectomy (N = 681). Complication rates, community costs of LC and OC groups, incidence of preoperative ERCP and/or intra-operative cholangiography as well as interventions for complications were studied. Incidence of cholecystectomy related BDI was 0.37% in LC, 2.81% in OC and 0.58% overall. Average costs amounted to [symbol: see text] 1.721 for uneventful LC, [symbol: see text] 2.924 for uneventful OC, [symbol: see text] 7.250 for primary, intra-operatively detected and immediately treated BDI [symbol: see text] 9.258 for primary delayed BDI treatments, [symbol: see text] 6.076 for secondary BDI treatments and [symbol: see text] 10.363 for non-BDI abdomino-surgical complications. In conclusion BDI with cholecystectomy reveals to be a serious complication increasing the overall average cost factor ninefold if not detected intra-operatively, in which case the raise is only fourfold

Background Intratumoral heterogeneity reflects subclonal diversity and accounts for a variety of clinically defined phenotypes including the development of drug resistance and recurrence. However, intratumoral heterogeneity of bileduct carcinoma (BDC) is rarely studied. Methods Two highly heterogeneous cell lines named EH-CA1a and EH-CA1b were established from a primary tumor tissue of a pathologically proven BDC. Distinct heterogeneity and underlying mechanisms of two cell lines in karyotype, colony formation, tumorgenicity, and sensitivity to chemoradiotherapy were intensively studied. Results Both cell lines showed typical morphology of cancer cells. EH-CA1a cells grew as free-floating aggregates, while EH-CA1b cells grew adherently as a monolayer. EH-CA1a cells had higher cloning efficiencies and were able to keep proliferating under hypoxic condition. Coincidentally, hypoxia-induced factor-1α (HIF1α) and vascular endothelial growth factor (VEGF) mRNA were significantly higher in EH-CA1a cells than in EH-CA1b cells. Both cell lines were tumorigenic in nude mouse, however, EH-CA1a cells showed more aggressive characteristics. Most importantly, the EH-CA1a cells showed much more resistance against radiation and chemotherapy with gemcitabine. Metastasis-related genes including matrix metalloproteinase 2 (MMP-2), MMP-9, epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail, and Twist, are more highly expressed in EH-CA1a cells than in EH-CA1b cells. Moreover, the percentage of cells expressing cancer stem cell-like marker, CD133, in EH-CA1a cells is much higher than that in EH-CA1b cells. Moreover, knockdown of CD133 in both EH-CA1a and EH-CA1b cells significantly reduced their invasive potential and increased their sensitivities to radiation and gemcitabine, suggesting the differential expression of CD133 protein may partially account for the difference in malignancy between these two cancer cells. Conclusion Establishment of these two cell

Kupffer cells (KCs), the liver resident macrophages accounting for 80–90% of the total population of fixed tissue macrophages in the body, not only play a key role in host defense via removing particulate materials from the portal circulation, but may also contribute to the pathogenesis of various liver diseases. We have previously demonstrated that KCs play an important role in controlling portal hypertension and hepatocellular injury via releasing thromboxane A2 (TXA2) in early fibrosis induced by one-week bileduct ligation (BDL). Production of TXA2 is controlled by cytosolic phospholipase A2 (cPLA2) that is activated by the interaction of entothelin-1 (ET-1) with its G-protein coupled ET receptor B (ETBR). However, the signaling pathways that contribute to the ET-1-induced activation of cPLA2 and production of TXA2 in KCs in the normal healthy or injured livers are not yet clear, which are investigated in the present study using isolated KCs from one-week BDL or sham rats. The pharmacological inhibition of cPLA2 or chelation of intracellular calcium abrogated the ET-1 induction of TXA2 from KCs. Compared to those from sham rats, KCs from BDL animals displayed a significantly enhanced responsiveness of p38 MAPK to ET-1, increased ETBR and Gαi subunit but decreased Gαq and Gα11 expression. Inhibition of ERK1/2 or Gq signaling abrogated significantly the ET-1 induction of TXA2 in sham KCs but only slightly in BDL KCs. In contrast, inhibition of p38 MAPK and Gi signaling markedly attenuated the ET-1 induction of TXA2 in BDL KCs but had no effect in sham KCs. Lastly, inhibition of PLC or PKC abrogated ET-1 induction of TXA2 in KCs from both sham and BDL groups. The hepatic stress (such as BDL) induces significant modifications in the receptor and intermediates of ET-1 signaling in KC and subsequently alters ET-1 signaling mechanisms, particularly a shift from Gq induced signaling to Gi induced signaling, in the activation of cPLA2 and production of TXA2 in

Background & aims: Oleanolic acid is abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb for the treatment of jaundice. However, the hepatoprotective role of oleanolic acid in obstructive cholestasis and its underlying molecular mechanism are unclear. Methods: Normal rats and bileduct-ligated (BDL) rats were given oleanolic acid and serum biochemistry, bile salts, and pro-inflammatory factors were measured, as well as the expression levels of liver bile acid synthesis and detoxification enzymes, membrane transporters, nuclear receptors, and transcriptional factors. Results: Oral administration of oleanolic acid at 100 mg/kg did not cause rat liver injury. However, it significantly reduced the serum levels of alanine aminotransferase (ALT) on days 7 and 14, aspartate aminotransferase (AST) and TNF-α on day 14, and alkaline phosphatase (ALP) and IL-1β on days 3, 7, and 14 in the BDL rats. Furthermore, the serum levels of total bile acid (TBA) and bile acids, including CDCA, CA, DCA, and Tα/βMCA were significantly reduced by oleanolic acid on day 3 in the BDL rats. In addition, the expression levels of detoxification enzymes Cyp3a, Ugt2b, Sult2a1, Gsta1-2, and Gstm1-3, membrane transporters Mrp3, Mrp4, Ostβ, Mdr1, Mdr2, and Bsep, nuclear receptors Pxr, Vdr, Hnf4α, Rxrα, Rarα, Lxr, and Lrh-1, and transcriptional factors Nrf2, Hnf3β, and Ahr were significantly increased in oleanolic acid-treated rats. Conclusion: We demonstrated that the oral administration of oleanolic acid attenuates liver injury, inflammation, and cholestasis in BDL rats. The anti-cholestatic effect may be associated with the induction of hepatic detoxification enzymes and efflux transporters mediated by nuclear receptors and transcriptional factors. PMID:25932098

The pharmacokinetics of TDP223206 was studied following single intravenous and oral administrations in rats. A mixture of TDP223206 and (14)C-TDP223206 were administered to intact and bileduct-cannulated rats. Following intravenous administration, plasma concentrations declined biphasically. The AUC(inf) increased linearly with dose but was not dose proportional. The PK parameters of TDP223206 indicated low clearance (254-386 ml/h/kg) and a moderate volume of distribution (968-1883 ml/kg). The bioavailability was 32.95% and 24.46% for 10 and 50 mg/kg oral doses, respectively. (14)C-TDP223206 was distributed widely into different tissues with small intestine, liver, kidneys and large intestine having large tissue to plasma ratios. (14)C-TDP223206 was the major circulating component in the plasma. A total of 91.2% of administered radioactivity of (14)C-TDP223206 was recovered in bile indicating that biliary excretion was the major pathway for drug elimination. (14)C-TDP223206-acyl glucuronides were the major metabolites in bile. The oxo-(14)C-TDP223206 was the major metabolite in plasma and an important metabolite in bile. Two forms of diastereomeric acyl glucuronides of (14)C-TDP223206 were detected in bile with similar LC/MS intensities suggesting a similar biotransformation capacity. Only one form of these (14)C-TDP223206-acyl glucuronides was detected in plasma suggesting that enterohepatic recirculation was related to the nature of the stereo-isomers. PMID:18260095

Background Colorectal liver metastases (CRLMs) with biliary invasion can be treated with a combined liver and extrahepatic bileduct resection. The aim of this study was to analyze outcomes of this procedure in a case-cohort analysis and systematic review. Methods Consecutive patients who underwent a major liver resection for CRLM between 2003 and 2013 were selected from a single center prospective database, comparing patients with and without biliary invasion. A specific and a general search strategy were used to identify relevant articles in the systematic review. Results Ten patients (13.2%) underwent combined liver and extrahepatic bileduct resection for CLRM with biliary invasion, among 76 patients included. An R0 resection was achieved in five of ten patients (50%); one of ten patients died postoperatively. Median overall survival was 19 months among patients with biliary invasion, versus 106 months among patients without biliary invasion (P=0.12). The systematic review yielded a large variability in 5-year survival after resection of CLRM with biliary invasion, ranging between 33–80%. Conclusions Surgical resection of CLRM with central biliary invasion is feasible, but survival in these patients tends to be lower due to a high rate of non-radical resections. PMID:27500147

When access to a major duodenal papilla or endoscopic retrograde cholangiopancreatography has failed, percutaneous transhepatic cholangioscopic lithotripsy (PTCS-L) may be useful for removing common bileduct (CBD) stones. However, the feasibility and usefulness of percutaneous transhepatic papillary large-balloon dilation (PPLBD) during PTCS-L for the removal of large CBD stones has not been established. We aimed to determine the safety and efficacy of PPLBD for the treatment of large CBD stones. Eleven patients with large CBD stones in whom the access to the major papilla or bileduct had failed were enrolled prospectively. Papillary dilation was performed using a large (12-20 mm) dilation balloon catheter via the percutaneous transhepatic route. Post-procedure adverse events and efficacy of the stone retrieval were measured. The initial success rate of PPLBD was 100%. No patient required a basket to remove a stone after PPLBD. Electrohydraulic lithotripsy was required in 2 (18.2%) patients. The median time to complete stone removal after PPLBD was 17.8 min and no adverse events occurred after PPLBD. Asymptomatic hyperamylasemia was not encountered in any patients. This study indicates that PPLBD is safe and effective for removal of large CBD stones. PMID:25729250

X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bileduct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bileducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis. PMID:26212186

Primary hepatolithiasis is a common bileduct disease with benign nature but complicated mechanisms. Current studies have revealed its correlation with cytokine release by chronic inflammation, which also increased mucin (MUC) synthesis. This study investigated the role of p38 mitogen-activated protein kinase (MAPK) in regulating cytokine release and mucin synthesis, in an attempt to elucidate the role of p38 signaling molecule in the pathogenesis of hepatolithiasis. In human intrahepatic bileduct endothelial cells (HIBECs), lipoprotein (LPS) was used to induce the high expression of MUC. Small interference RNA (siRNA) was then used to silencing p38 gene expression. Cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured, along with MUC5AC protein and mRNA expression assay. The interference of p38 gene expression inhibited the release of IL-1β and TNF-α in cultured cells. It also depressed both mRNA and protein levels of MUC5A. P38 MAPK signal pathway may be involved in the formation and progression of hepatolithiasis. This study provides potential new strategy for treating hepatolithiasis using p38 MAPK signal pathway as the drug target. PMID:26722604

X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bileduct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bileducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis.

Interferon-alpha2b (IFN) is known to prevent and to reverse experimental liver fibrosis and damage. S-Adenosyl-L-methionine (SAM) is a well-known hepatoprotective substance. The aim of the present work was to determine the effect of the administration of both drugs simultaneously to bileduct-ligated rats. Administration of IFN (50000 IU s.c.) and/or SAM (10 mg kg[-1] i.m.) began 15 days after biliary obstruction and continued for a further 15 days. The liver was used for glycogen and collagen quantification. Bilirubins and enzyme activities were measured in serum. Either SAM or IFN ameliorated all markers of liver damage studied. However, when administered together their beneficial effects were markedly reduced. It is not possible to explain the antagonistic effect of these compounds on liver damage with the present data. More studies are needed to determine SAM-IFN interactions. PMID:9570697

Studies in animal models allow identifying mechanisms and treatments for cognitive and motor alterations in hepatic encephalopathy (HE). Liver diseases leading to HE in humans have different aetiologies (alcoholic, viral, etc.). The International Society for Hepatic Encephalopathy points out that satisfactory model for HE resulting from alcoholic cirrhosis are lacking. This work aimed to develop and characterize an animal model for HE in alcoholic liver cirrhosis. To potentiate the effects of alcohol on liver we administered it (5, 8 or 10% in drinking water) to rats showing mild liver damage induced by "mild" bileduct ligation (MBDL), obtained by sectioning 3 out of 5 bileducts. MBDL rats show increased markers of cholestasis and liver damage, hyperammonemia and inflammation. MBDL rats also show motor in-coordination, hypokinesia, impaired learning ability in a Y maze and reduced spatial memory in the Morris water maze. Ingesting 10% ethanol does not induce relevant liver damage in control rats but potentiates liver damage in MBDL rats. In contrast, ethanol did not enhance the biochemical or neurological alterations in MBDL rats. This supports that the combination of certain levels of hyperammonemia and inflammation is enough to induce mild cognitive impairment, even in the absence of liver cirrhosis. Rats with MBDL and MBDL-OH survived more than 3 months, allowing performing long-term studies on cognitive and motor alterations and on underlying mechanisms. MBDL-OH rats are a good model to study the mechanisms of ethanol-induced liver cirrhosis and the factors making the liver susceptible to ethanol damage. PMID:24838616

Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bileduct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (~1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bileducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bileduct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions. PMID:23897680

An higher incidence rate of iatrogenic bileduct injuries is reported in cholecystectomy performed with the laparoscopy than with the laparotomy approach. The aim of this study was to provide a multicentre report on surgical treatment and the outcome of biliary complications during and following laparoscopic cholecystectomy. A questionnaire was mailed to all surgeons with experience in laparoscopic cholecystectomy in the Campania region. Data were collected from January 1991 to December 2003. Each patient was requested to indicate age, gender, associated diseases, site and type of lesion, surgical experience, diagnosis, treatment and complications. Twenty-six surgeons answered the questionnaire. Fifty-one patients (36 F/15 M; mean age: 42.5 +/- 11.9, range 13-91 years) with bileduct injuries following laparoscopic cholecystectomy were reported. The most frequent lesions were main bileduct partial or total transection. The intraoperative mortality rate was 1/51 (1.9%) due to a complex biliary and vascular injury. The postoperative mortality rate of revision surgery was 5/50 (10%). T-tube positioning (n = 20) and Roux-en-Y hepato-jejunostomy (n = 20) were the procedures most frequently performed. The complication rate in patients treated with the T-tube was significantly higher than in those treated with hepatico-jejunostomy. Surgical treatment of biliary injuries following laparoscopic cholecystectomy was characterized by unusually high mortality and morbidity for a non-neoplastic disease. Roux-en-Y hepato-jejunostomy remains the procedure of choice for these injuries. PMID:16060179

Aims. We here investigated the association of different types of periampullary diverticula (PAD) with pancreaticobiliary disease and with technical success of endoscopic retrograde cholangiopancreatography (ERCP). Methods. A total of 850 consecutive patients who underwent their first ERCP were entered into a database. Of these patients, 161 patients (18.9%) had PAD and the age- and sex-matched control group comprised 483 patients. Results. PAD was correlated with common bileduct (CBD) stones (59.6% versus 35.0% in controls; P = 0.008) and negatively correlated with periampullary malignancy (6.8% versus 21.5% in controls; P = 0.004). The acute pancreatitis was more frequent (62.5%) in patients with PAD type 1 followed by PAD type 2 (28.9%, P = 0.017) and type 3 (28.0%, P = 0.006). No significant differences were observed in successful cannulation rate and post-ERCP complications among the 3 types of PAD. Type 1 PAD patients had less recurrence of CBD stones than did the patients who had type 2 or type 3 PAD (53.8% versus 85.7%; P = 0.043). Conclusions. PAD, especially type 1 PAD, is associated with an increased acute pancreatitis as well as occurrence and recurrence of CBD stones. PAD during an ERCP should not be considered as an obstacle to a successful cannulation. PMID:27143965

Solitary duodenal Peutz-Jeghers (PJ)-type hamartomatous polyps are rare and considered a different disease entity than classic PJ syndrome. We describe the case of an 89-year-old man admitted to our emergency department with symptoms of acute cholangitis, liver dysfunction, and slight jaundice. Magnetic resonance imaging showed multiple signal voids, reflecting choledocholithiasis, and an oval-shaped tumor in the common bileduct (CBD). Following endoscopic retrograde cholangiopancreatography, the patient was diagnosed with a lower CBD tumor 20 mm in diameter. Endoscopic sphincterotomy was performed for choledocholithotomy, resulting in the expulsion of a large tumor with a stalk connected to the papilla of Vater. The tumor was successfully excised en bloc by endoscopic snare papillectomy. Histopathologic examination showed that the tumor was a PJ-type hamartomatous polyp. No mucocutaneous pigmentation of the skin was evident and the patient's family history was negative. Solitary duodenal PJ-type hamartomatous polyps are usually diagnosed incidentally during endoscopy for other indications because most of these tumors are asymptomatic or have nonspecific presentations. To our knowledge, this is the first reported solitary PJ-type polyp with intra-CBD growth treated by endoscopic snare papillectomy. PMID:26185397

Background: Bileduct injury (BDI) is a severe complication that may arise during the surgical treatment of benign disease and a few patients will develop end-stage liver disease (ESLD) requiring a liver transplant (LT). Objective: Analyse the experience using LT as a definitive treatment of BDI in Argentina. Patients and Methods: A national survey regarding the experience of LT for BDI. Results: Sixteen out 18 centres reported a total of 19 patients. The percentage of LT for BDI from the total number of LT per period was: 1990–94 = 3.1%, 1995–99 = 1.6%, 2000–04 = 0.7% and 2005–09 = 0.2% (P < 0.001). The mean age was 45.7 ± 10.3 years (range 26–62) and 10 patients were female. The BDI occurred during cholecystectomy in 16 and 7 had vascular injuries. One patient presented with acute liver failure and the others with chronic ESLD. The median time between BDI and LT was 71 months (range 0.2–157). The mean follow-up was 8.3 years (10 months to 16.4 years). Survival at 1, 3, 5 and 10 years was 73%, 68%, 68% and 45%, respectively. Conclusions: The use of LT for the treatment of BDI declined over the review period. LT plays a role in selected cases in patients with acute liver failure and ESLD. PMID:21762297

Liver fibrosis represents a frequent event following chronic insult to trigger wound healing responses in the liver. Activation of hepatic stellate cells (HSCs), which is a pivotal event during liver fibrogenesis, is accompanied by enhanced expressions of a series of marker proteins and pro-fibrogenic signaling molecules. Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb Artemisia annua L., and can inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to attenuate lung injury and fibrosis. However, the effect of DHA on liver fibrosis remains unclear. The aim of this study was to investigate the effect of DHA on bileduct ligation-induced injury and fibrosis in rats. DHA improved the liver histological architecture and attenuated collagen deposition in the fibrotic rat liver. Experiments in vitro showed that DHA inhibited the proliferation of HSCs and arrested the cell cycle at the S checkpoint by altering several cell-cycle regulatory proteins. Moreover, DHA reduced the protein expressions of a-SMA, α1 (I) collagen and fibronectin, being associated with interference of the platelet-derived growth factor β receptor (PDGF-βR)-mediated ERK pathway. These data collectively revealed that DHA relieved liver fibrosis possibly by targeting HSCs via the PDGF-βR/ERK pathway. DHA may be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis. PMID:27038258

Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bileduct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

Bileduct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes, resulting in dilutional hyponatremia due to increased water intake and vasopressin release. This project tested the hypothesis that angiotensin signaling at the subfornical organ (SFO) augments drinking behavior in BDL rats. A genetically modified adeno-associated virus containing short hairpin RNA (shRNA) for ANG II receptor subtype 1a (AT1aR) gene was microinjected into the SFO of rats to knock down expression. Two weeks later, BDL or sham surgery was performed. Rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. The rats were euthanized 28 days after BDL surgery for analysis. A group of rats was perfused for immunohistochemistry, and a second group was used for laser-capture microdissection for analysis of SFO AT1aR gene expression. BDL rats showed increased water intake that was attenuated in rats that received SFO microinjection of AT1aR shRNA. Among BDL rats treated with scrambled (control) and AT1aR shRNA, we observed an increased number of vasopressin-positive cells in the supraoptic nucleus that colocalized with ΔFosB staining, suggesting increased vasopressin release in both groups. These results indicate that angiotensin signaling through the SFO contributes to increased water intake, but not dilutional hyponatremia, during congestive liver failure. PMID:25009217

There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bileduct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin (R2 = 0.8450, P = 3.04e − 12). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD. PMID:27212785

Background—Endoscopic papillary balloon dilatation (EPBD) has been reported as a safe and effective alternative to endoscopic sphincterotomy in the management of common bileduct (CBD) stones; its effect on papillary function has yet to be elucidated. Aim—To investigate sphincter of Oddi (SO) motility before and after EPBD to determine its effect on SO function. Patients and methods—The papillary function of 10 patients with CBD stones was studied using endoscopic manometry before and one week after EPBD. The manometric studies were repeated one month after EPBD in seven patients. Results—One week after EPBD, CBD pressure, SO peak pressure, SO basal pressure, and SO frequency decreased significantly. One month after EPBD, however, all parameters increased although the increases in SO basal pressure and CBD pressure were not significant. There was no significant difference in values of any parameter before and one month after EPBD. No serious complications occurred. Conclusion—These data suggest at least partial recovery of papillary function one month after the procedure. EPBD seems to preserve papillary function in treatment of CBD stones; a longer term follow up study with SO manometry should be performed to clarify the effect of EPBD on SO function. Keywords: endoscopic papillary balloon dilatation; sphincter of Oddi PMID:9391256

The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bile-duct epithelial cells (cholangiocytes) as bile passes through bileducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology. PMID:18837079

Aim: Liver failure is associated with dyshomeostasis of efflux transporters at the blood-brain barrier (BBB), which contributes to hepatic encephalopathy. In this study we examined whether breast cancer resistance protein (BCRP), a major efflux transporter at the BBB, was altered during liver failure in rats. Methods: Rats underwent bileduct ligation (BDL) surgery, and then were sacrificed after intravenous injection of prazosin on d3, d7 and d14. The brains and blood samples were collected. BCRP function at the BBB was assessed by the brain-to-plasma prazosin concentration ratio; Evans Blue extravasation in the brain tissues was used as an indicator of BBB integrity. The protein levels of BCRP in the brain tissues were detected. Human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) were tested in vitro. In addition, hyperbilirubinemia (HB) was induced in rats by intravenous injection of unconjugated bilirubin (UCB). Results: BDL rats exhibited progressive decline of liver function and HB from d3 to d14. In the brain tissues of BDL rats, both the function and protein levels of BCRP were progressively decreased, whereas the BBB integrity was intact. Furthermore, BDL rat serum significantly decreased BCRP function and protein levels in HCMEC/D3 cells. Among the abnormally altered components in BDL rat serum tested, UCB (10, 25 μmol/L) dose-dependently inhibit BCRP function and protein levels in HCMEC/D3 cells, whereas 3 bile acids (CDCA, UDCA and DCA) had no effect. Similar results were obtained in MDCK-BCRP cells and in the brains of HB rats. Correlation analysis revealed that UCB levels were negatively correlated with BCRP expression in the brain tissues of BDL rats and HB rats as well as in two types of cells tested in vitro. Conclusion: UCB elevation in BDL rats impairs the function and expression of BCRP at the BBB, thus contributing to hepatic encephalopathy. PMID:27180978

To mimic the excretion route of the quinolone antibacterial agent levofloxacin (LVFX) in humans, we produced an excretion-limited (EL) model in male Sprague-Dawley rats by bileduct ligation and unilateral nephrectomy. We then examined the relationship between brain levels of LVFX and its convulsant effects in control and EL animals. Serum concentrations of LVFX in EL animals (EL + LVFX) were 2.38- and 1.59-fold and brain concentrations were 1.33- and 1.19-fold those of the controls (control + LVFX) at 30 min after a single intravenous injection of 10 and 100 mg/kg LVFX, respectively. Furthermore EL animals became more susceptible to the convulsant effect of LVFX with a 1.28-fold decrease in convulsion-inducing dose. In combination with oral pretreatment with 400 mg/kg 4-biphenylacetic acid (BPAA), convulsion-inducing doses in the control (control + LVFX + BPAA) and EL (EL + LVFX + BPAA) groups were markedly decreased by 2.25 and 9 times that of the control + LVFX group. EL operation and BPAA pretreatment slowed the elimination of LVFX in the serum and brain 4 hr later in the following order: EL + LVFX + BPAA, control + LVFX + BPAA, EL + LVFX, and control + LVFX groups. This order reflects that for the convulsion-inducing doses. These results suggest that EL rats may be a useful model for humans and that the convulsant effect of LVFX with or without BPAA arises not only from the attainment of maximum brain concentration but also from delayed disappearance from the brain. PMID:8742326

Backgrounds and study aims: Endoscopic sphincterotomy (ES) is widely accepted as first-line therapy for bileduct stones (BDS). The major long-term pancreaticobiliary complication is BDS recurrence. Whether cholecystectomy should be performed after ES, especially in elderly patients, remains controversial. The aim of this study is to investigate the short-term and long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for BDS and to analyze risk factors for pancreaticobiliary complications. We also compared long-term outcomes in patients older and younger than age 80. Patients and methods: A total of 1210 patients who underwent therapeutic ERCP for BDS were retrospectively reviewed to identify risk factors for pancreaticobiliary complications. We divided these patients into two groups: Group Y (

Bileduct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes including peripheral vasodilation and generalized edema. Peripheral vasodilation is hypothesized to then activate compensatory mechanisms including increased drinking behavior and neurohumoral activation. This study tested the hypothesis that changes in the expression of AT1R mRNA and protein in the lamina terminalis is associated with BDL induced hypoosmolality in the rat. All rats received either BDL or sham ligation surgery. The rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. Angiotensin type 1 receptor (AT1R) expression in the lamina terminalis was assessed by western blot and quantitative real-time PCR (RT-qPCR). Average baseline water intake significantly increased in BDL rats compared to sham and upregulation of AT1R protein and AT1aR mRNA were observed in the subfornical organ (SFO) of BDL rats. Separate groups of BDL and sham ligated rats were instrumented with minipumps filled with either losartan (2.0 µg/µl) or 0.9% saline for chronic intracerebroventricular (ICV) or subcutaneous (SC) chronic infusion. Chronic ICV losartan infusion attenuated the increased drinking behavior and prevented the increased abundance of AT1R protein in the SFO in BDL rats. Chronic SC did not affect water intake or AT1R abundance in the SFO. The data presented here indicate a possible role of increased central AT1R expression in the regulation of drinking behavior during congestive cirrhosis. PMID:23243146

Background/Aims: Endoscopic papillary balloon dilation (EPBD) is a possible alternative to endoscopic sphincterotomy (EST) for common bileduct (CBD) stones. To date, 10- and 8-mm EPBD have not been fully compared. Patients and Methods: Patients who underwent EPBD for CBD stones at two Japanese tertiary care centers between May 1994 and January 2014 were identified. Matched pairs with 10- and 8-mm EPBD were generated. Short- and long-term outcomes were compared between the two groups. Results: A total of 869 patients were identified (61 and 808 patients for 10- and 8-mm EPBD, respectively), and 61 well-balanced pairs were generated. The rate of complete stone removal within a single session was higher in the 10-mm EPBD group than in the 8-mm EPBD group (69% vs. 44%, P < 0.001), and use of lithotripsy was less frequent in the 10-mm EPBD group (23% vs. 56%, P < 0.001). The rates of post-ERCP pancreatitis were similar between the 10- and 8-mm EPBD groups (11% vs. 8%). Cumulative biliary complication-free rates were not statistically different between the two groups: 88% [95% confidence interval (CI): 79–97%] and 94% (95% CI: 88–100%) at 1 year and 69% (95% CI: 56–85%) and 80% (95% CI: 69–93%) at 2 years in the 10- and 8-mm EPBD groups, respectively. In the 10-mm EPBD group, ascending cholangitis was not observed, and pneumobilia was found in 5% of cases during the follow-up period. Conclusions: EPBD using a 10-mm balloon for CBD stones is safe and more effective than 8-mm EPBD. The sphincter function is highly preserved after 10-mm EPBD. PMID:26228364

Highlights: •HB-EGF expression was increased during the development of liver fibrosis. •Conditional HB-EGF knockout mouse showed enhanced experimental liver fibrosis. •HB-EGF antagonized TGF-β-induced activation of hepatic stellate cells. •We report a possible protective role of HB-EGF in cholestatic liver fibrosis. -- Abstract: Our aims were to evaluate the involvement of heparin-binding EGF-like growth factor (HB-EGF) in liver fibrogenesis of humans and mice and to elucidate the effect of HB-EGF deficiency on cholestatic liver fibrosis using conditional HB-EGF knockout (KO) mice. We first demonstrated that gene expression of HB-EGF had a positive significant correlation with that of collagen in human fibrotic livers, and was increased in bileduct ligation (BDL)-induced fibrotic livers in mouse. We then generated conditional HB-EGF knockout (KO) mice using the interferon inducible Mx-1 promoter driven Cre recombinase transgene and wild type (WT) and KO mice were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen, compared with WT mice. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. Interestingly, HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis.

Biliary tract carcinomas are relatively rare, representing less than 1% of cancers. However, their incidence has increased in Japan and in industrialized countries like the USA. Biliary tract tumors have a poor prognosis and a high mortality rate because they are usually detected late in the course of the disease; therapeutic treatment options are often limited and of minimal utility. Recent studies have shown the importance of serum and molecular markers in the diagnosis and follow up of biliary tract tumors. This review aims to introduce the main features of the most important serum and molecular markers of biliary tree tumors. Some considerable tumor markers are cancer antigen 125, carbohydrate antigen 19-9, carcinoembryonic antigen, chromogranin A, mucin 1, mucin 5, alpha-fetoprotein, claudins and cytokeratins. PMID:21528090

Limy bile syndrome is a rare condition in which the gallbladder is filled with a paste-like radiopaque material. The presence of limy bile in the common bileduct is rare. A 72-year-old woman was admitted to our hospital with epigastric pain and jaundice. Plain abdominal radiography on admission showed a radiopaque material in the gallbladder. Computed tomography also showed that the gallbladder and the common bileduct were filled with a radiopaque material. The patient had never received any cholecystographic contrast agents. As a result, a diagnosis of obstructive jaundice due to choledocholithiasis, which includes limy bile, was made. We herein report the process by which limy bile syndrome, complicated by obstructive jaundice, was successfully treated through combined treatment via endoscopic sphincterotomy and laparoscopic cholecystectomy. PMID:20480840

Less than complete cholecystectomy has been advocated for difficult operative conditions for more than 100 years. These operations are called partial or subtotal cholecystectomy, but the terms are poorly defined and do not stipulate whether a remnant gallbladder is created. This article briefly reviews the history and development of the procedures and introduces new terms to clarify the field. The term partial is discarded, and subtotal cholecystectomies are divided into "fenestrating" and "reconstituting" types. Subtotal reconstituting cholecystectomy closes off the lower end of the gallbladder, reducing the incidence of postoperative fistula, but creates a remnant gallbladder, which may result in recurrence of symptomatic cholecystolithiasis. Subtotal fenestrating cholecystectomy does not occlude the gallbladder, but may suture the cystic duct internally. It has a higher incidence of postoperative biliary fistula, but does not appear to be associated with recurrent cholecystolithiasis. Laparoscopic subtotal cholecystectomy has advantages but may require advanced laparoscopic skills. PMID:26521077

Background/Aims Endoscopic retrograde cholangiopancreatography (ERCP) can be an effective treatment for bile leakage after liver transplantation. We evaluated the efficacy of endoscopic treatment in liver transplantation in patients who developed bile leaks. Methods Forty-two patients who developed bile leaks after liver transplantation were included in the study. If a bile leak was observed on ERCP, a sphincterotomy was performed, and a nasobiliary catheter was then inserted. If a bile leak was accompanied by a bileduct stricture, either the stricture was dilated with balloons, followed by nasobiliary catheter insertion across the bileduct stricture, or endoscopic retrograde biliary drainage was performed. Results In the bile leakage alone group (22 patients), endoscopic treatment was technically successful in 19 (86.4%) and clinically successful in 17 (77.3%) cases. Among the 20 patients with bile leaks with bileduct strictures, endoscopic treatment was technically successful in 13 (65.0%) and clinically successful in 10 (50.0%) cases. Among the 42 patients who underwent ERCP, technical success was achieved in 32 (76.2%) cases and clinical success was achieved in 27 (64.3%) cases. Conclusions ERCP is an effective and safe therapeutic modality for bile leaks after liver transplantation. ERCP should be considered as an initial therapeutic modality in post-liver transplantation patients. PMID:25717048

Ascariasis is a common helminthic disease worldwide, although Lithuania and other European countries are not considered endemic areas. The presence of the Ascaris worm in the biliary tree causes choledocholithiasis-like symptoms. We report a case of pancreatic duct ascariasis causing such symptoms. A 73-year-old Lithuanian woman underwent endoscopic retrograde cholangiopancreatography (ERCP) suspecting choledocholithiasis. Contrast injection into the common bileduct demonstrated a slightly dilated biliary tree without any filling defects, and the tail of an Ascaris worm protruding from the opening of the papilla Vater. The worm was captured by a snare but escaped deep into the duct. After a small wirsungotomy the worm was retrieved from the pancreatic duct. The patient received a 150 mg dose of levamisole orally repeated 7 days later and was discharged after complete resolution of symptoms. This first reported sporadic case of pancreatic duct ascariasis in Lithuania was successfully treated with ERCP and Levamisole. PMID:26374772

Background and Objectives: Endoscopic ultrasound (EUS) achieves results comparable to endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of common bileduct (CBD) stone, but studies from the western have shown EUS to be less expensive in patients with intermediate risk for CBD stones. The aim of this study was to compare the costs of EUS and ERCP in the diagnosis of CBD stones in a developing country. Materials and Methods: A prospective study was done with 141 patients with suspected CBD stones, categorized as having high or intermediate risk for CBD stone. All underwent EUS, and the high-risk patients had ERCP after the EUS. For intermediate-risk patients, an ERCP was done at the discretion of the attending physician. The CBD stone was confirmed by ERCP in patients who underwent both EUS and ERCP. Patients who received EUS only were followed up every 3 months for 1 year. The false negative rate in patients with EUS and ERCP was estimated in the clinical follow-up. Result: One hundred and forty-one patients (141: 83 females, 58 males) with a mean age ± standard deviation (SD) of 55.71 ±18.68 years were recruited. Ninety-four (94) patients underwent both EUS and ERCP. ERCP confirmed the diagnosis in 83 of 85 patients (97.6%) with CBD stone detected by EUS. Forty-seven (47) patients with a negative EUS and no ERCP done were symptom-free during the follow-up. The overall sensitivity, specificity, positive predictive value, and negative predictive value of EUS were 97.6%, 80%, 97.6%, and 80% respectively. An EUS-based strategy for high-risk patients was 15% more expensive than an ERCP-based strategy, but the EUS-based strategy reduced the cost to 37.78% less than the ERCP-based strategy in intermediate-risk patients. The EUS-based strategy was cost-saving when the CBD stone prevalence was less than 52.5%. Conclusion: EUS is safer and less costly than ERCP for CBD stone diagnosis in patients with intermediate risk. PMID:27386473

Background Malignancies arising from the biliary tract can arise from the epithelial lining of the biliary tract and surrounding tissues. Conditions that predispose to malignancy as well as preneoplastic changes in biliary tract epithelia have been identified. In this overview, we discuss preneoplastic conditions of the biliary tract and emphasize their clinical relevance. Results Chronic biliary tract inflammation predisposes to cancer in the biliary tract. Biliary tract carcinogenesis involves a multistep process as a consequence of chronic biliary epithelial injury or inflammation. Reminiscent of other gastrointestinal epithelial malignancies such as gastric, colon, and pancreatic cancer, biliary tract cancers may evolve via a multistep progression from epithelial hyperplasia and dysplasia to malignant transformation. The potential role of initiating cells is also becoming recognized. Conclusions In spite of improved risk factor recognition, and advances in diagnostic tools, the early diagnosis of pre-malignant or malignant biliary tract conditions is extremely challenging, and there is a paucity of evidence on which to base their management. As a result, the role of pre-emptive surgery remains largely undefined. PMID:22391777

... removed completely. Palliative surgery is not expected to cure the cancer, but it can sometimes help a person feel ... an option. In some cases it might even cure the cancer. But even for people who are eligible for ...

A lensing duct to condense (intensify) light using a combination of front surface lensing and reflective waveguiding is described. The duct tapers down from a wide input side to a narrow output side, with the input side being lens-shaped and coated with an antireflective coating for more efficient transmission into the duct. The four side surfaces are uncoated, preventing light from escaping by total internal reflection as it travels along the duct (reflective waveguiding). The duct has various applications for intensifying light, such as in the coupling of diode array pump light to solid state lasing materials, and can be fabricated from inexpensive glass and plastic. 3 figures.

A lensing duct to condense (intensify) light using a combination of front surface lensing and reflective waveguiding. The duct tapers down from a wide input side to a narrow output side, with the input side being lens-shaped and coated with an antireflective coating for more efficient transmission into the duct. The four side surfaces are uncoated, preventing light from escaping by total internal reflection as it travels along the duct (reflective waveguiding). The duct has various applications for intensifying light, such as in the coupling of diode array pump light to solid state lasing materials, and can be fabricated from inexpensive glass and plastic.

Background & aims Small duct primary sclerosing cholangitis (PSC) is phenotypically a mild version of large duct PSC, but it is unknown whether these phenotypes share aetiology. We aimed to characterize their relationship by investigating genetic associations in the HLA complex, which represent the strongest genetic risk factors in large duct PSC. Methods Four classical HLA loci (HLA-A, HLA-B, HLA-C, HLA-DRB1) were genotyped in 87 small duct PSC patients, 485 large duct PSC patients and 1117 controls across three geographical regions. Results HLA-DRB1*13:01 (OR=2.0, 95% CI 1.2–3.4, P=0.01) and HLA-B*08 (OR=1.6, 95% CI 1.1–2.4, P=0.02) were significantly associated with small duct PSC compared with healthy controls. Based on the observed frequency of HLA-B*08 in small duct PSC, the strongest risk factor in large duct PSC, an estimated 32% (95% CI 4%–65%) of this population can be hypothesized to represent early stages or mild variants of large duct PSC. This subgroup may be constituted by small duct PSC patients with inflammatory bowel disease (IBD), which greatly resembled large duct PSC in its HLA association. In contrast, small duct PSC without IBD was only associated with HLA-DRB1*13:01(P=0.03) and was otherwise distinctly dissimilar from large duct PSC. Conclusions Small duct PSC with IBD resembles large duct PSC in its HLA association and may represent early stages or mild variants of large duct disease. Different HLA associations in small duct PSC without IBD could indicate that this subgroup is a different entity. HLA-DRB1*13:01 may represent a specific risk factor for inflammatory bileduct disease. PMID:24517468

Intraductal papillary neoplasm of the bileduct (IPNB) is a variant type of the bileduct carcinoma characterized by intraductal growth. IPNB is also recognized as a precursor of invasive carcinoma. We describe herein an extremely rare case of IPNB arising from the cystic duct. A 68-year-old man was admitted to our hospital for investigation of epigastralgia and abnormal levels of biliary tract enzyme. Computed tomography and magnetic resonance imaging showed a mass lesion spreading from the cystic duct to the upper-middle bileduct. Endoscopic retrograde cholangiography demonstrated diffuse duct dilation with a grossly visible intraductal mass and amorphous blobs, suggesting the presence of mucobilia or scattered tumors. We performed extrahepatic bileduct resection with lymphadenectomy. Macroscopically, a friable papillary tumor originated from the cystic duct grows intraluminally into the bileduct. Pathologically, the tumor was found to be intramucosal adenocarcinoma spreading to the whole extrahepatic bileduct, which was compatible with IPNB. We should discuss the features and progression processes of IPNB through this precious case.

1. The effect of etofibrate, the ethandiol-1,2 diester of nicotinic and clofibric acids on bile production was studied in male rats that received a daily dose of 300 mg of etofibrate/kg body weight by stomach tube for 10 days and were compared with control rats receiving the medium. 2. The bileduct was cannulated, animals were intravenously given 1 microCi (4-14C)-cholesterol/100 b.w. and bile was collected at different intervals for a total of 4 hr. 3. Etofibrate treatment decreased plasma cholesterol and triglyceride concentrations and increased the bile flow. The cummulative amount of both bile volume and total bile radioactivity secreted increased linearly in all the animals; the respective slopes being higher in etofibrate treated rats than in controls. 4. The main labelled component found in the bile was always bile acids rather than cholesterol and the proportion of each of these compounds was similar in both groups. Neither was any difference between the groups found in the concentration of bile acids, cholesterol and phospholipids nor in the cholesterol/(bile+phospholipid) ratio. 5. Besides other factors, the present results indicate that an increase in bile flow and biliary cholesterol excretion in its free form and after its conversion into bile acids should contribute to the hypocholesterolemic effect of etofibrate. PMID:7789727

Bile secretory failure (cholestasis) may result from several possible mechanisms involved in bile secretion. We have examined the possibility that abnormalities in enzyme content, composition, and turnover of liver plasma membrane constituents are altered in cholestasis. Severe and mild cholestasis were produced by 5 days of bileduct ligation and ethinyl estradiol administration, respectively. Bileduct ligation but not ethinyl estradiol treatments was associated with elevations of the serum bilirubin level and 5′-nucleotidase activity. However, basal bile flow and bilirubin transport maximum (Tm) were significantly reduced after ethinyl estradiol treatment. Liver plasma membrane fractions rich in canalicular membranes were prepared from groups of rats in each of three categories; normal, after bileduct ligation, or ethinyl estradiol administration, and their respective controls. Electron microscopy and enzyme marker studies demonstrated plasma membrane fractions free of significant contamination. Plasma membrane fractions prepared from mild as well as severe cholestasis had increased alkaline phosphatase activity, and reduced 5′-nucleotidase and Mg2+-ATPase activities. Co2+-CMPase activity was unchanged. Kinetic analysis of 5′-nucleotidase and Mg2+-ATPase activities in plasma membrane fractions demonstrated reduced Vmaz (but unaltered Km). Reducted Vmaz was unrelated to addition in vitro of di-or trihydroxy bile salts or ethinyl estradiol and, therefore, suggests that reduced activities in cholestasis are due to decreased enzyme content. Cholestasis was not associated with changes in the synthesis or degradation rate of pulse-labeled plasma membrane proteins or alterations in the major protein bands separated on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Plasma membrane cholesterol, phospholipid, and neutral sugar content was unaltered, but sialic acid content was significantly increased in both forms of cholestasis. Alterations in

Chylomicrons prevent endotoxin toxicity and increase endotoxin uptake by hepatocytes. As a consequence, less endotoxin is available to activate macrophages, thereby reducing tumor necrosis factor secretion. To determine whether the chylomicron-mediated increase in hepatocellular uptake of endotoxin results in increased endotoxin excretion into bile, we examined bile after endotoxin administration. A sublethal dose (7 micrograms/kg) of 125I-endotoxin was incubated with either rat mesenteric lymph containing nascent chylomicrons (500 mg of chylomicron triglyceride per kg of body weight) or an equal volume of normal saline (controls) for 3 h and then infused into male Sprague-Dawley rats. Bile samples were collected via a common bileduct catheter for 24 h. Infusion of endotoxin incubated with chylomicrons increased biliary excretion of endotoxin by 67% at 3 h (P < or = 0.006) and by 20% at 24 h (P < or = 0.01) compared with infusion of endotoxin incubated in saline. Endotoxin activity, as measured by the Limulus assay, was not detected in the bile of test animals. However, endotoxin activity was detected after hot phenol-water extraction of bile, demonstrating that endotoxin is inactive in the presence of bile but retains bioactivity after hepatic processing. Since the majority of an intravenous endotoxin load has been shown to be cleared by the liver, acceleration of hepatocyte clearance and biliary excretion of endotoxin may represent a component of the mechanism by which chylomicrons protect against endotoxin-induced lethality. PMID:8335381

A closure for an inclined duct having an open upper end and defining downwardly extending passageway. The closure includes a cap for sealing engagement with the open upper end of the duct. Associated with the cap are an array of vertically aligned plug members, each of which has a cross-sectional area substantially conforming to the cross-sectional area of the passageway at least adjacent the upper end of the passageway. The plug members are interconnected in a manner to provide for free movement only in the plane in which the duct is inclined. The uppermost plug member is attached to the cap means and the cap means is in turn connected to a hoist means which is located directly over the open end of the duct.

The paper presents an experimental study of pathological human bile taken from the gallbladder and bileducts. The flow dependences were obtained for different types of bile from patients with the same pathology, but of different age and sex. The parameters of the Casson's and Carreau's equations were found for bile samples. Results on the hysteretic bile behavior at loading-unloading tests are also presented, which proved that the pathologic bile is a non-Newtonian thixotropic liquid. The viscosity of the gallbladder bile was shown to be higher compared to the ductbile. It was found that at higher shear stress the pathological bile behaves like Newtonian fluid, which is explained by reorientation of structural components. Moreover, some pathological bile flow in the biliary system CFD simulations were performed. The velocity and pressure distributions as well as flow rates in the biliary segments during the gallbladder refilling and emptying phases are obtained. The results of CFD simulations can be used for surgeons to assess the patient's condition and choose an adequate treatment.

Background Bile leak is a common and serious complication of cholecystectomy with endotherapy being an established method of treatment. This retrospective study presents the 11-year experience of a referral center in endoscopic management of post-cholecystectomy bile leaks. Methods During the period between January 2000 and December 2010, records of patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP) for suspected post-cholecystectomy bile leaks were reviewed for evidence of clinical presentation of bile leaks, cholangiographic findings, type of endoscopic intervention, procedural complications and post-procedure follow-up. Results Seventy-one patients with suspected post-cholecystectomy bile leak were referred for ERCP. Common bileduct (CBD) cannulation was successful in 70 patients (98.59%). Complete transection of CBD was diagnosed in 4 patients; they were treated with surgery. A leak from the cystic duct stump was demonstrated in 49 patients (74.24%), from the ducts of Luschka in 4 (6.06%), from the gallbladder bed in 2 (3.03%), from the CBD in 7 (10.61%) and from the common hepatic duct (CHD) in 4 patients (6.06%). Endoscopic sphincterotomy (ES) plus endoprosthesis was performed in 64 patients (96.97%). A 12-year-old girl with a leak from cystic duct stump was successfully treated with stenting without ES and one patient with leak from gallbladder bed underwent only ES. Endoscopic intervention failed to treat a leak from CHD in one patient. During the follow-up, three patients developed bileduct stricture. Two were treated endoscopically and one with hepaticojejunostomy. Conclusions ES plus large-bore straight plastic biliary stent placement is a safe and effective intervention in post-cholecystectomy bile leaks. PMID:24713781

In liver and intestine, transporters play a critical role in maintaining the enterohepatic circulation and bile acid homeostasis. Over the past two decades, there has been significant progress toward identifying the individual membrane transporters and unraveling their complex regulation. In the liver, bile acids are efficiently transported across the sinusoidal membrane by the Na+ taurocholate cotransporting polypeptide with assistance by members of the organic anion transporting polypeptide family. The bile acids are then secreted in an ATP-dependent fashion across the canalicular membrane by the bile salt export pump. Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. The bile acids are shuttled across the enterocyte to the basolateral membrane and effluxed into the portal circulation by the recently indentified heteromeric organic solute transporter, OSTα-OSTβ. In addition to the hepatocyte and enterocyte, subgroups of these bile acid transporters are expressed by the biliary, renal, and colonic epithelium where they contribute to maintaining bile acid homeostasis and play important cytoprotective roles. This article will review our current understanding of the physiological role and regulation of these important carriers. PMID:19498215

Research requiring the murine pancreatic duct to be imaged is often challenging due to the difficulty in selectively cannulating the pancreatic duct. We have successfully catheterized the pancreatic duct through the common bileduct in severe combined immune deficient (SCID) mice and imaged the pancreatic duct with gas filled lipid microbubbles that increase ultrasound imaging sensitivity due to exquisite scattering at the gas/liquid interface. A SCID mouse was euthanized by CO2, a midline abdominal incision made, the common bileduct cut at its midpoint, a 2 cm, 32 gauge tip catheter was inserted about 1 mm into the duct and tied with suture. The duodenum and pancreas were excised, removed in toto, embedded in agar and an infusion pump was used to instill normal saline or lipid-coated microbubbles (10 million / ml) into the duct. B-mode images before and after infusion of the duct with microbubbles imaged the entire pancreatic duct (~ 1 cm) with high contrast. The microbubbles were cavitated by high mechanical index (HMI) ultrasound for imaging to be repeated. Our technique of catheterization and using lipid microbubbles as a contrast agent may provide an effective, affordable technique of imaging the murine pancreatic duct; cavitation with HMI ultrasound would enable repeated imaging to be performed and clustering of targeted microbubbles to receptors on ductal cells would allow pathology to be localized accurately. This research was supported by the Experimental Mouse Shared Service of the AZ Cancer Center (Grant Number P30CA023074, NIH/NCI and the GI SPORE (NIH/NCI P50 CA95060).

A length of longitudinally extending duct assembly for heated corrosive gases includes an outer support duct and a substantially gas-tight liner. The liner is spaced from the outer support duct by a relatively yielding spacer material that accommodates expansion of the liner in directions parallel to the inner surface of the outer support duct and in directions normal to the inner surface of the outer support duct without imposing any substantial resistance to such thermal expansion.

Around the world, Ascaris lumbricoides is the most common helminthic infection. We describe the case of a 25-year-old woman, known to have had Ascaris infestation, presenting with abdominal pain, constipation and jaundice together with fever and tachycardia. There was tenderness in the right hypochondrium and liver function tests confirmed cholestatic jaundice. An abdominal ultrasound showed multiple linear echogenic foci in the distal small intestine along with cholelithiasis and a thick-walled gall bladder with a single stone compressing the common bileduct (Mirizzi syndrome). The patient underwent exploratory laparotomy; more than 100 worms were found inside the small intestine and they were removed by enterotomy and manual decompression. No worm could be palpated within the common bileduct (CBD). Cholecystectomy was performed, during which an accessory cystic duct was noted opening into the common bileduct superiorly to the main cystic duct. A 10 cm live worm was found coming out of it and was removed via forceps. Later on an endoscopic retrograde cholangio-pancreatogram (ERCP) showed a widened ampulla, a mildly dilated common bileduct, but without any filling defects. The patient made an uneventful postoperative recovery being discharged on the ninth day. Worms in an accessory cystic duct have not been report in the medical literature so far. PMID:25430551

Patient: Male, 82 Final Diagnosis: Retroperitoneal biloma due to spontaneous perforation of the left hepatic duct Symptoms: Abdominal pain • high fever Medication: — Clinical Procedure: Emergent operation Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Spontaneous perforation of the bileduct in adults is very rare, particularly in cases accompanied by retroperitoneal biloma. We report a patient with retroperitoneal biloma due to a spontaneous perforation of the left hepatic duct. Case Report: An 82-year-old man was admitted to our institution with abdominal pain and a high fever. He had tenderness at the epi-mesogastrium. Computed tomography showed several stones in the gall bladder and common bileduct (CBD) and a few ascites. A substantial amount of fluid had collected from the dorsal stratum of the duodenum and pancreas head to the right paracolic gutter and anterior side of the right iliopsoas. Laboratory examination revealed a high inflammation score. He underwent emergent laparotomy. Biliary fluid was revealed after the mobilization of the pancreas head, duodenum, and right side of the colon. Bileduct perforation was suspected. Therefore, we exfoliated the dorsal side of the CBD to the cranial side, and intraoperative cholangiography was performed. However, the perforation site could not be detected. Cholecystectomy and choledocholithotomy were performed. A retrograde transhepatic biliary drainage tube was inserted, and primary closure of the CBD incision site was achieved. Postoperative cholangiography revealed leakage from the left hepatic duct near the caudate branch. Conclusions: There are a few reports of spontaneous bileduct perforation cases in the literature, particularly on infants or children with congenital anomalies, but it is rare in adults. It usually causes bile peritonitis, although bileduct perforation should be considered in the differential diagnosis of spontaneous retroperitoneal fluid collection in

Context and Objective: Accessory pancreatic duct (APD) designed to reduce the pressure of major pancreatic duct by forming a secondary drainage channel. Few studies have mentioned the variant types of accessory ducts and their mode of formation, some of these have a clear clinical significance. Present study is aimed to evaluate the possible variations in the APD and its terminations. Materials and Methods: Forty formalin fixed adult human pancreas with duodenum in situ specimens were studied by injecting 1% aqueous eosin, followed by piece meal dissection of the head of the pancreas from posterior surface. Formation, tributaries, relations, and the termination of the accessory pancreatic duct were noted and photographed. Results: Accessory ducts revealed 50% belonged to long type, 22.5% were of short and ansa pancreatica type each, and embryonic type of duct pattern was seen in 5% specimens. 75% of long type ducts showed positive patency with eosin dye, followed by ansa type (44.4%), and least patency was found in short type (22.2%). With regard to the patency of the accessory pancreatic ducts towards their termination, we found 52.5% of the accessory ducts and 5% of the embryonic type pancreatic ducts were patent and in 42.5% of the specimen the ducts were obliterated. In 85% of specimens the minor duodenal papillae was anterosuperior to the major papilla and superior to the major papillae in 10% of the cases, and in 5% minor papillae was absent. The average distance between the two papillae was 2.35 cm. Conclusion: The knowledge of the complex anatomical relations of the gland with its duct, duodenum and bileducts are essential for the surgeons and sinologists to plan and perform both the diagnostic as well as therapeutic procedures effectively. PMID:25954609

Bile acid homeostasis is tightly maintained through interactions between the liver, intestine, and kidney. During cholestasis, the liver is incapable of properly clearing bile acids from the circulation, and alternative excretory pathways are utilized. In obstructive cholestasis, urinary elimination is often increased, and this pathway is further enhanced after bileduct ligation in mice that are genetically deficient in the heteromeric, basolateral organic solute transporter alpha-beta (Ostα-Ostβ). In this study, we examined renal and intestinal function in Ostα-deficient and wild-type mice in a model of bile acid overload. After 1% cholic acid feeding, Ostα-deficient mice had significantly lower serum ALT levels compared with wild-type controls, indicating partial protection from liver injury. Urinary clearance of bile acids, but not clearance of [3H]inulin, was significantly higher in cholic acid-fed Ostα-deficient mice compared with wild-type mice but was not sufficient to account for the protection. Fecal excretion of bile acids over the 5 days of cholic acid feeding was responsible for almost all of the bile acid loss in Ostα-deficient mice, suggesting that intestinal losses of bile acids accounted for the protection from liver injury. Thus fecal loss of bile acids after bile acid overload reduced the need for the kidney to filter and excrete the excess bile acids. In conclusion, Ostα-deficient mice efficiently eliminate excess bile acids via the feces. Inhibition of intestinal bile acid absorption might be an effective therapeutic target in early stages of cholestasis when bile acids are still excreted into bile. PMID:21719738

Bile acid homeostasis is tightly maintained through interactions between the liver, intestine, and kidney. During cholestasis, the liver is incapable of properly clearing bile acids from the circulation, and alternative excretory pathways are utilized. In obstructive cholestasis, urinary elimination is often increased, and this pathway is further enhanced after bileduct ligation in mice that are genetically deficient in the heteromeric, basolateral organic solute transporter alpha-beta (Ostα-Ostβ). In this study, we examined renal and intestinal function in Ostα-deficient and wild-type mice in a model of bile acid overload. After 1% cholic acid feeding, Ostα-deficient mice had significantly lower serum ALT levels compared with wild-type controls, indicating partial protection from liver injury. Urinary clearance of bile acids, but not clearance of [(3)H]inulin, was significantly higher in cholic acid-fed Ostα-deficient mice compared with wild-type mice but was not sufficient to account for the protection. Fecal excretion of bile acids over the 5 days of cholic acid feeding was responsible for almost all of the bile acid loss in Ostα-deficient mice, suggesting that intestinal losses of bile acids accounted for the protection from liver injury. Thus fecal loss of bile acids after bile acid overload reduced the need for the kidney to filter and excrete the excess bile acids. In conclusion, Ostα-deficient mice efficiently eliminate excess bile acids via the feces. Inhibition of intestinal bile acid absorption might be an effective therapeutic target in early stages of cholestasis when bile acids are still excreted into bile. PMID:21719738

A duct joining system for providing an air-tight seal and mechanical connection for ducts and fittings is disclosed. The duct joining system includes a flexible gasket affixed to a male end of a duct or fitting. The flexible gasket is affixed at an angle relative to normal of the male end of the duct. The female end of the other duct includes a raised bead in which the flexible gasket is seated when the ducts are properly joined. The angled flexible gasket seated in the raised bead forms an air-tight seal as well as fastens or locks the male end to the female end. Alternatively, when a flexible duct is used, a band clamp with a raised bead is clamped over the female end of the flexible duct and over the male end of a fitting to provide an air tight seal and fastened connection.

A duct joining system for providing an air-tight seal and mechanical connection for ducts and fittings is disclosed. The duct joining system includes a flexible gasket affixed to a male end of a duct or fitting. The flexible gasket is affixed at an angle relative to normal of the male end of the duct. The female end of the other duct includes a raised bead in which the flexible gasket is seated when the ducts are properly joined. The angled flexible gasket seated in the raised bead forms an air-tight seal as well as fastens or locks the male end to the female end. Alternatively, when a flexible duct is used, a band clamp with a raised bead is clamped over the female end of the flexible duct and over the male end of a fitting to provide an air tight seal and fastened connection.

Background & aims Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. Methods We studied experimental cholestatic liver disease induced by bileduct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2−/− mice. Results Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2−/− mice than wild type mice following bileduct ligation for 3 weeks. In contrast to wild type mice, Nod2−/− mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. Conclusions Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte. PMID:24560660

Bile acid synthetic defects (BASD), uncommon genetic disorders that are responsible for approximately 2% of persistent cholestasis in infants, are reviewed with emphasis on morphology of associated liver disease. The associated liver diseases may be life threatening, and are treatable, usually by replacement of deficient primary bile acids. Specific diagnosis is made by analysis of body fluids (bile, blood, and urine) using fast atom bombardment-mass spectroscopy (FAB-MS) and gas chromatography-mass spectroscopy (GC-MS). Inborn errors have been demonstrated for four single enzymes involved in modification of the sterol nucleus and in five steps in modification of the side-chain to form cholic and chenodeoxycholic acids, the primary bile acids. With few exceptions, BASD cause liver diseases that vary from severe to mild depending on the defect. In three of four known defects of sterol nucleus modification, liver disease is progressive. Progression of liver disease is most rapid when the defect results in accumulation of toxic monohydroxy and unsaturated oxo-bile acids. Liver disease may be transient, delayed in onset and mild. Reduced bile flow caused by atypical bile acids contributes to cholestasis and may be the dominant factor in defects of side-chain synthesis, peroxisomal abiogenesis and S-L-O syndrome. Pathological findings may include intralobular cholestasis with giant cell transformation, prevalence of necrotic hepatocytes including giant cell forms, and hepatitic injury confined to the portal limiting plate where the smallest bile ductules may be injured and where fibrosis typically develops. Interlobular bileducts are usually spared. Ultrastructure of liver reveals nonspecific changes with the possible exception of unusual canalicular morphology in some defects. The course of BASD may be modified by replacement of deficient primary bile acids, which produces beneficial feedback inhibition of abnormal bile acid production and enhances choluresis. Giant

Non-sulfated bile acid levels including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), five taurine conjugates, and five glycine conjugates in duodenal juice were measured in 50 Chinese infants with cholestasis to test their diagnostic value. All 17 with biliary atresia (BA) cases, 11 out of 26 neonatal hepatitis (NH) cases and one case with paucity of the interlobular bileduct were without detectable bile acids. In those NH patients with detectable bile acids, the major components were conjugated forms of CA and CDCA, which was similar to all 6 cases of the comparison group with other diseases. The minor bile acid components identified in them were glycine conjugated UDCA, free CDCA, free CA, and free and conjugated DCA. Only one patient with NH had taurine conjugated LCA. The mean total duodenal bile acid level in 15 patients with NH was significantly lower than that in the 6 patients of the comparison group. Most patients with NH had a CDCA/CA ratio of less than one, indicating that cholic acid is the predominant form in their bile. Glycine conjugated bile acids were the predominant bile acids present in 11 out of 15 patients with NH and 4 out of 6 of the comparison group patients. The results suggest that the detection of duodenal bile acids by a sensitive HPLC method is of limited value in making a differential diagnosis between BA and NH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1680988

Nicotine and its major metabolite cotinine inhibit alpha-hydroxylation of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) suggesting that an alternative pathway of NNK metabolism and elimination, biliary excretion of the O-glucuronide of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL-Gluc) may be enhanced. To verify the possible role of cotinine on biliary elimination of NNK and its metabolites, bileduct cannulated rats were administered a single i.p. dose of 50 mg/kg [56sup;-3 H]-NNK with or without i.p. co-administration of 5 mg/kg cotinine or nicotine. Cotinine significantly reduced cumulative bile flow and biliary elimination of NNK-derived radioactivity within six hours to 42 and 27 percent, respectively. The pattern of NNK metabolites in bile was unchanged. Nicotine had a similar inhibitory effect on bile flow. This result constitutes the first experimental evidence that cotinine inhibits bile flow. In rats, biliary elimination of NNK is reduced accordingly which may lead to an increased carcinogen burden in the body. In humans, inhibition of bile flow by tobacco alkaloids may contribute to the appetite suppressing effect of tobacco products. PMID:10882639

... tract. A specimen of bile is placed in culture media and observed for growth of microorganisms. If there ... no infection. If there is growth in the culture media, the growth is then isolated and identified to ...

The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bileduct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP inhibitors and therefore potential cholestasis perpetrators. PMID:26642869

The authors present 12 cases of true malignant ampulloma and 23 cases of carcinoma of the biliary tract (MBT). They analyze frequency, symptomatology, pathology, radiology, treatment and results. They stress that decreasing malignancy is in the following order: cancer of the MBT, cancer of the gallbladder, and ampulloma. The latter is the least lethal with the most long-term cures. As to cancer of the MBT no cure is to be expected, but palliative surgery (resection or tumor by-pass) will bring temporary cure; consequently this should always be tried when possible despite the high operative mortality. PMID:1114872

Evolutionary processes have not yet developed specific and safe ways to detoxify all chemical species new to our environment. Indeed, some are transformed and/or conjugated by the liver into more toxic species. Environmental factors can modulate hepatic enzyme systems. Particularly responsive are the mixed function oxidases, which initiate the transformation of many xenobiotics to excretable species via reactions which generate electrophilic intermediates such as free radicals, epoxides and aldehydes. Unless these reactive metabolites are rapidly removed by subsequent detoxification reactions or by endogenous defense systems, destructive cytotoxic reactions can be triggered or cell constitutents “attacked” thereby causing either acute injury and/or more latent molecular injury to long chain biopolymers resulting in chromatin damage, or tumors. In vitro systems using purified, specialized cell fractions may be of considerable value in defining metabolic processes, but the results must be relevant to in vivo conditions. Although human liver is peculiarly resistant to tumorigenesis, liver microsomes (isolated endoplasmic reticulum) are extensively used as biological activators for in vitro mutagenicity test systems. The in vivo defense system of liver cells must be exceptionally efficient! Reactive metabolites generated in liver may be stable enough to migrate and cause injury to other tissues or organ systems. It is important to characterize metabolic pathways of toxic xenobiotics, subsequent molecular sites or modes of injury, and factors which depress or augment cellular defense systems including the biliary system responsible for the excretion of many xenobiotics. Only then can techniques or treatments be developed to screen individuals for risk to specific groups of xenobiotics, to protect those exposed, and to treat those injured. PMID:598341

... at a Glance Show More At a Glance Estimated New Cases in 2016 39,230 % of All New Cancer Cases 2.3% Estimated Deaths in 2016 27,170 % of All Cancer ... of This Cancer : In 2013, there were an estimated 54,954 people living with liver and intrahepatic ...

The effects of bileduct ligation (BDL), choledochostomy, bile acid sequestering within the intestinal lumen by cholestyramine, and fluid and electrolyte replacement on survival time and development of diarrhea after whole-body exposure to doses of ionizing radiation that result in death from acute intestinal injury were studied. BDL significantly prolonged survival and delayed the onset of diarrhea after exposure to /sup 137/Cs gamma rays, fission neutrons, or cyclotron-produced neutrons in the range of doses that produce intestinal death or death from a combination of intestinal and hematopoietic injuries. Cannulation of the bileduct with exteriorized bile flow (choledochostomy) to protect the irradiated intestine from the mucolytic action of bile salts did not duplicate the effect of BDL in increasing survival time. Choledochostomy without fluid replacement eliminated the occurrence of diarrhea in 15.4 Gy irradiated rats. Diarrhea did occur in irradiated animals with choledochostomy if they received duodenal injections of fluid and electrolytes to replace the fluid lost as a result of bile drainage. Duodenal injection of fluid and electrolytes had no significant effect on survival time in irradiated rats. Injection of fluid and electrolytes into the peritoneal cavity of irradiated rats resulted in an increase in survival time that was comparable to that observed after BDL. Addition of antibiotics to the peritoneally injected fluid and electrolytes further increased survival time (up to 9 days). This survival time approached that seen in animals receiving the same radiation dose but which had the intestine exteriorized and shielded to minimize radiation injury to the intestine. Postmortem histological examinations of the irradiated small intestine showed mucosal regeneration in these long-term survivors receiving fluid and antibiotic therapy.

Pancreatic stents are used for a variety of conditions during therapeutic endoscopic retrograde cholangio pancreatography (ERCP). Pancreatic duct stenting reduces the incidence of post-ERCP pancreatitis and facilitate bilitary cannulation in difficult cases. Proximal migration of a pancreatic stent during bileduct stone extraction is an infrequent event, but its management can be technically challenging. We present a case that a double flanged pancreatic stent (5 French (Fr), 5 cm) was placed to facilitate the bilitary cannulation during the bileduct stone extraction. The pancreatic duct stent migrated into the proximal pancreas duct at the end of the bileduct stone clearance. After two unsuccessful attempts to remove the impacted stent with a balloon catheter and forceps, wire-guided endoscopic snare retrieval was conducted. Firstly, a guide wire was placed in the pancreatic duct and a soft mini-snare was passed over the guide wire. Then, the mini-snare was advanced into the proximal pancreatic duct over the guide wire and the proximally migrated stent was removed successfully with the mini-snare. Wire-guided endoscopic snare retrieval of proximally migrated pancreatic stents is safe and effective. The successful case of the retrieval with mini-snare provides another option for proximal migration retrieval of pancreatic stent retrieval. Further studies are needed to confirm its effectiveness and elucidate its associated complications. PMID:24714023

The establishment of novel bile ductular cell cultures was accomplished with the use of explants of a hyperplastic bile ductular tissue preparation obtained from rat livers at 10 to 15 weeks after bileduct ligation or a bile ductular cell fraction isolated from this tissue preparation by a procedure involving Percoll density gradient centrifugation. Observations made on these primary explant and monolayer bile ductular cell cultures were limited to the first 3 days of culture where the morphologic features of the bile ductular epithelium remained fairly well preserved, while fibroblast contamination was found to be very low. These cultured cells also retained over this period a high specific activity for the bile ductular cell marker enzyme gamma-glutamyl transpeptidase, as well as possessed measurable but decreasing specific activities for leucine aminopeptidase and alkaline phosphatase. Karyotypic analysis of the cultured monolayer cells further showed them to be diploid. In addition, preliminary transplantation studies demonstrated the presence of well-differentiated bile ductular-like structures following inoculation of the freshly isolated bile ductular cell fraction into the interscapular fat pads of recipient rats. Images Figure 2 Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2861743

Bile acid sequestrants are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can ... block them. These medicines work by blocking bile acid in your stomach from being absorbed in your ...

A phospholipase C in bile, free of bacterial infection, has recently been identified from cholesterol gallstone patients. Because of the importance of phosphatidylcholine in solubilizing cholesterol in bile, this study further investigates the metabolism of phosphatidylcholine in delipidated gallbladder and common bileductbiles. Phospholipase C activity, as measured by the release of phosphoryl[3H]choline from the substrate 1,2-dipalmitoyl-sn-glycero-3-phospho [N-methyl-3H]choline, was identified in both hepatic and gallbladder biles. Similar levels of activity (nmol.h-1.mg-1 of delipidated protein) were found in common bileduct (11.25 +/- 14.23) and gallbladder bile (19.07 +/- 22.24), although per milliliter of bile, the mean gallbaldder levels were 6.4 times greater than those found in common ductbile. With the tow substrates, 1-palmitoyl-2[9,10-3H] palmitoyl-sn-glycero-3-phosphocholine and 1,2(1-14C) dipalmitoyl-sn-glycero-3-phosphocholine, the majority of organically extracted label, after thin-layer chromatography, was recovered as radiolabeled diglyceride, confirming the presence of phospholipase C. Diglyceride levels were found to be closely correlated with [3H]choline (slope, 0.9820; r = 0.9844). In addition to diglyceride, both radiolabeled free fatty acid and monoglyceride were identified in common bileduct and gallbladder biles, although their levels were an order of magnitude less than measurable phospholipase C activity. To determine whether the free fatty acid release was due to either a diacylglycerol-lipase or a phospholipase A2, the effect of adding unlabeled diglyceride on free fatty acid formation from the substrate [14C]DPPC was examined. As the concentration of unlabeled diglyceride was increased, the amount of free fatty acid and monoglyceride released were both reduced in parallel. Direct measurement of diacylglycerol-lipase activity by incubating the diglyceride, sn-2[3H]dipalmitoyl, resulted in release of both products in a ratio

Bile stone disease is one of the most prevalent gastroenterological diseases with a considerable geographical and ethnic variation. Bile stones can be classified according their origin, their localization and their biochemical structure. Development and clinical expression depend on a complex interaction between congenital and acquired risk factors. Indeed, bile stones can be either asymptomatic, or cause biliary colic or complications such as acute cholecystitis, jaundice, cholangitis and acute pancreatitis. Diagnosis is based on a combination of clinical features, laboratory findings and imaging techniques and correct identification of symptomatic gallstone patients is essential before cholecystectomy. Transabdominal ultrasonography is the gold standard for the diagnosis of gallstones. However, endoscopic ultrasonography, magnetic resonance cholangiopancreatography and intraoperative cholangiography may also play a role in the diagnosis of bile stones. Management includes prevention measures against modifiable risk factors. Biliary colic and acute cholecystitis are common indications of laparoscopic cholecystectomy, while endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy and stone extraction is the gold standard for the treatment of common bileduct (CBD) stones. Timing of ERCP and cholecystectomy are of critical importance in the management. Lithotripsy modalities are generally reserved for patients with technically difficult CBD stone removal. Percutaneous access combined with lithotripsy may be helpful for complicated intrahepatic stones. PMID:26771377

Expanding balloon serves as lightweight emergency valve to close wide duct. Uninflated balloon stored in housing of duct. Pad resting on burst diaphragm protects balloon from hot gases in duct. Once control system triggers valve, balloon inflates rapidly to block duct. Weighs much less than does conventional butterfly, hot-gas, or poppet valve capable of closing duct of equal diameter.

The effects of high doses of ursodeoxycholic acid on bile acid composition and the liver morphology was examined in 60 male Syrian golden hamsters. The animals were allocated to five groups: I, control; II and IV received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 30 days and III and V received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 60 days. Bile acids were determined by high performance liquid chromatography. In all treated groups there was a significant increase in chenodeoxycholic and lithocholic acid in the bile. The mean glyco/tauro ratio was significantly higher than in the control group, reaching values > 1 for individual bile acids, except for lithocholic acid values which remained < 1. Under light microscopy, the livers of the hamsters showed damage which was dose/time related, namely portal inflammatory infiltrate, bileduct proliferation, cholestasis, fat infiltration and necrosis. Electron microscopy revealed pronounced changes starting with microvilli edema and extending to canalicular membrane destruction and necrosis. The changes observed in the relation glyco/tauro lithocholic acids, may be due to defence mechanisms to avoid hepatotoxicity. The hepatotoxicity resulting from ursodeoxycholic acid administration is presumed to be due primarily to lithocholic acid or some lithocholic acid metabolite. PMID:8058592

Cystic duct cysts are a rare congenital anomaly. While the other bileduct cysts (choledochus and the intrahepatic bileducts) are classified according to the classification described by Tadoni, there is no classification method described by the cystic duct cysts, although it is claimed that the cystic duct cysts may constitute a new "Type 6" category. Only a limited number of patients with cystic duct cysts have been reported in the literature. The diagnosis is usually made in the neonatal period or during childhood. The clinical symptoms are nonspecific and usually include pain in the right upper quadrant and jaundice. The condition may also present with biliary colic, cholangitis, cholelithiasis, or pancreatitis. In our case, the abdominal ultrasonography (US) performed on a 6-year-old female patient who presented with pain in the right upper quadrant pointed out an anechoic cyst at the neck of the gall bladder. Based on the magnetic resonance cholangiopancreatography (MRCP) results, a cystic dilatation was diagnosed in the cystic duct. The aim of this case-report presentation was to discuss the US and MRCP findings of the cystic dilatation of cystic duct, which is an extremely rare condition, in the light of the literature information. PMID:24987540

Duct leakage has been identified as a major source of energy loss in residential buildings. Most duct leakage occurs at the connections to registers, plenums or branches in the duct system. At each of these connections a method of sealing the duct system is required. Typical sealing methods include tapes or mastics applied around the joints in the system. Field examinations of duct systems have typically shown that these seals tend to fail over extended periods of time. The Lawrence Berkeley National Laboratory has been testing sealant durability for several years. Typical duct tape (i.e. fabric backed tapes with natural rubber adhesives) was found to fail more rapidly than all other duct sealants. This report summarizes the results of duct sealant durability testing of five UL 181B-FX listed duct tapes (three cloth tapes, a foil tape and an Oriented Polypropylene (OPP) tape). One of the cloth tapes was specifically developed in collaboration with a tape manufacturer to perform better in our durability testing. The first test involved the aging of common ''core-to-collar joints'' of flexible duct to sheet metal collars, and sheet metal ''collar-to-plenum joints'' pressurized with 200 F (93 C) air. The second test consisted of baking duct tape specimens in a constant 212 F (100 C) oven following the UL 181B-FX ''Temperature Test'' requirements. Additional tests were also performed on only two tapes using sheet metal collar-to-plenum joints. Since an unsealed flexible duct joint can have a variable leakage depending on the positioning of the flexible duct core, the durability of the flexible duct joints could not be based on the 10% of unsealed leakage criteria. Nevertheless, the leakage of the sealed specimens prior to testing could be considered as a basis for a failure criteria. Visual inspection was also documented throughout the tests. The flexible duct core-to-collar joints were inspected monthly, while the sheet metal collar-to-plenum joints were inspected

The hypothesis has been tested that postcholecystectomy common duct stones of the brown subtype are a consequence of three factors: bile infection, old age and previous sphincterotomy. It was found that: (i) 27 of 39 consecutive patients with recurrent common duct stones had brown stones. Nineteen of these 27 patients (70.3%) had previous sphincterotomy or sphincteroplasty: (ii) six of 15 patients with stone and bile analysis both at the time of cholecystectomy and at the second operation and who had sterile operative bile and non brown stones at the first operation, formed brown stones after T-tube drainage and after the onset of bile infection; (iii) patients with both intra and postoperative negative bile culture (n = 39 out of 137) had a lower mean age (50.5 years) and less frequently had a sphincterotomy than did individuals with a negative culture at operation, who subsequently had bile infection (n = 37; mean age 58.5 years; sphincterotomy in 88.8% of cases). In addition, in a follow up study of 105 patients with sphincterotomy and with sphincteroplasty (including ERCP or i.v. cholangiography in all cases), mean follow-up interval 6.1 years, 11.3 % of patients had brown recurrent common duct stones. It is suggested that, since brown recurrent common duct stones are secondary to bile stasis and infection and the duodenum is going to be colonized by bacteria with increasing age, sphincterotomy (and subsequent stricture), facilitating bile contamination and bacterial overgrowth, could be one of the major determinants of brown recurrent common duct stones (RCS) formation. In particular, more than 11% of the patients with a sphincterotomy are going to form in the future RCS of the brown subtype. PMID:1810368

Certain discrete, intense wave signals attributed to auroral kilometric radiation (AKR) were observed with ISEE-l while it was within the plasmaspheric shadow zone for direct propagation. It is believed that wave ducting by thin depletions of the plasma density aligned with the magnetic field accounts for such signals, and that their discrete nature is caused by the satellite intercepting individual ducts. These ducts, which were also observed as coincident decreases of the upper hybrid resonance frequency, appeared to be twenty-percent depletions roughly one hundred kilometers across. The AKR, which is emitted approximately perpendicular to the magnetic field, apparently entered these ducts equatorward of the source after the waves had been refracted parallel to the duct axis. A diffuse background was also observed which is consistent with the leakage from similar ducts at lower L-values. These observations establish the existence of ducted AKR, its signature on the satellite wave spectrograms, and new evidence for depletion ducts within the plasmasphere.

On October 16, 1992, during a routine examination of the loft of Building 332, the Building Coordinator observed cracks in the welds of the duct work that services the fume hoods for Rooms 1313, 1321, and 1329. Further examination revealed cracks in the weld of the duct work that services the gloveboxes in Rooms 1321 and 1329. Upon discovery of the cracked welds, facility management immediately took the following two actions: Because one crack in the fume hood exhaust extended 70% around the duct circumference, a 1-ton chain fall was used to secure the duct to the roof support structure to prevent the duct from falling if the duct completely fractured. The Facility Manager suspended plutonium handling operations in the gloveboxes and work in the fume hoods in the affected rooms until the situation could be thoroughly investigated. Building 332 is ventilated by drawing conditioned air from the building hallways into the laboratories, hoods, and gloveboxes. This air is filtered through two sets of high-efficiency particulate air (HEPA) filters before being exhausted from the facility. Figure 1 is a schematic of the typical air flow pattern for the facility. All affected duct work is located in the loft of the facility or pressure zone 4. This ducting is fabricated from 12-, 14- and 16-gauge, 304 stainless-steel sheet stock and joined by the Gas Tungsten Arc Welding (GTAW) process.

The purpose of this study was to evaluate if a rat model, based upon co-administration of the anion-exchanging resin, cholestyramine, could replace surgery when evaluating the importance of bile on drug absorption. Two different formulations were used for the administration of halofantrine; polyethylene glycol 400 (PEG 400) and PEG 400/polysorbate 80 (50:50, w/w%), as a positive and negative control on the dependency of bile. No significant effect of the resin was detected after evaluation of three different pre-dosing regimes, but in line with previous studies the formulation containing polysorbate 80 showed a significant increase in the absorption of halofantrine. This study therefore demonstrates that the pre-dosing of rats with Cholestyramine can not replace surgical bileduct cannulation if a formulation needs to be evaluated for its bile dependency. PMID:22732256

Total and hexavalent chromium were measured in bile samples obtained from cannulated bileducts of male rats iv administered with potassium dichromate at various doses corresponding to 0.1, 0.5, and 1 mg of chromium. The evaluation of the hexavalent form was performed by separation with a liquid anion exchanger and electrothermal atomization-atomic absorption spectrophotometric determination. Within 2 hr 1.35-2.23% of the chromium injected was recovered in bile as total chromium, the hexavalent form accounting for less than 1% of the total chromium collected, which seems almost entirely excreted as trivalent chromium. Since Cr(VI) administered iv was quickly reduced to Cr(III) in blood, the possibility exists for chromium in trivalent form to penetrate into the liver cells and to be excreted in the bile, possibly by binding to a carrier such as the low-molecular-weight substances described by Yamamoto et al.

Double duct sign where there is a simultaneous dilatation of both the common bileduct (CBD) and pancreatic duct is usually associated with sinister causes like malignancies of pancreatic head or ampulla. Occasionally, benign causes like chronic pancreatitis or sphincter of Oddi dysfunction (SOD) may cause double duct sign. Chronic opium abuse is a rare cause of the double duct sign, and endoscopic ultrasound (EUS) findings of this rare entity have been occasionally reported. We report about a 54-year-old male with a history of chronic alcohol and opioid abuse evaluated for episodes of abdominal pain and found to have opioid-related SOD and improved with biliary sphincterotomy. EUS was done to rule out malignancy and revealed hypoechoic prominence around terminal CBD suggestive of hypertrophied muscle. PMID:27503161

Double duct sign where there is a simultaneous dilatation of both the common bileduct (CBD) and pancreatic duct is usually associated with sinister causes like malignancies of pancreatic head or ampulla. Occasionally, benign causes like chronic pancreatitis or sphincter of Oddi dysfunction (SOD) may cause double duct sign. Chronic opium abuse is a rare cause of the double duct sign, and endoscopic ultrasound (EUS) findings of this rare entity have been occasionally reported. We report about a 54-year-old male with a history of chronic alcohol and opioid abuse evaluated for episodes of abdominal pain and found to have opioid-related SOD and improved with biliary sphincterotomy. EUS was done to rule out malignancy and revealed hypoechoic prominence around terminal CBD suggestive of hypertrophied muscle. PMID:27503161

Patent arterial duct (PAD) is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area) is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of pulmonary overcirculation

Patent arterial duct (PAD) is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area) is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of pulmonary overcirculation

Mirizzi syndrome has been defined in the literature as common bileduct obstruction resulting from calculi within Hartmann's pouch or cystic duct. We present a case of a 78-year-old female, who developed postcholecystectomy Mirizzi syndrome from a remnant cystic duct stone. Diagnosis of postcholecystectomy Mirizzi syndrome was made on endoscopic retrograde cholangiography (ERCP) performed postoperatively. The patient was treated with a novel strategy by combining advanced endoscopic and laparoscopic techniques in three stages as follows: Stage 1 (initial presentation): endoscopic sphincterotomy with common bileduct stent placement; Stage 2 (6 weeks after Stage 1): laparoscopic ultrasonography to locate the remnant cystic duct calculi followed by laparoscopic retrieval of the calculi and intracorporeal closure of cystic duct stump; Stage 3 (6 weeks after Stage 2): endoscopic removal of common bileduct stent along with performance of completion endoscopic retrograde cholangiogram. In addition, we have performed an extensive review of the various endoscopic and laparoscopic management techniques described in the literature for the treatment of postcholecystectomy syndrome occurring from retained cystic duct stones. PMID:27047698

Mirizzi syndrome has been defined in the literature as common bileduct obstruction resulting from calculi within Hartmann's pouch or cystic duct. We present a case of a 78-year-old female, who developed postcholecystectomy Mirizzi syndrome from a remnant cystic duct stone. Diagnosis of postcholecystectomy Mirizzi syndrome was made on endoscopic retrograde cholangiography (ERCP) performed postoperatively. The patient was treated with a novel strategy by combining advanced endoscopic and laparoscopic techniques in three stages as follows: Stage 1 (initial presentation): endoscopic sphincterotomy with common bileduct stent placement; Stage 2 (6 weeks after Stage 1): laparoscopic ultrasonography to locate the remnant cystic duct calculi followed by laparoscopic retrieval of the calculi and intracorporeal closure of cystic duct stump; Stage 3 (6 weeks after Stage 2): endoscopic removal of common bileduct stent along with performance of completion endoscopic retrograde cholangiogram. In addition, we have performed an extensive review of the various endoscopic and laparoscopic management techniques described in the literature for the treatment of postcholecystectomy syndrome occurring from retained cystic duct stones. PMID:27047698

Mirizzi syndrome (MS) is a rare complication of chronic cholelithiasis, which is always caused by a calculus in the cystic duct or neck of the gallbladder, resulting in mechanical compression of common bileduct and the gallbladder. It is clinically characterized by abdominal pain, fever, as well as obstructive jaundice. During cholecystectomy, MS is seen as a dangerous adherent and inflammatory tissue in the area of Calot's triangle. In the general population, aberrant right posterior hepatic duct, one of the causes of bileduct injury during duct surgery, is present in 4.8%-8.4% of people. Herein we report a rare case of a 76-year-old female patient, with hepatolithiasis of right posterior lobe and cholecysto-aberrant right posterior hepatic duct fistula. This is a special type of MS; however, interestingly, she did not have any symptoms, and the disease was found by physical examination incidentally. This case highlights another situation, namely, there may be difficulty in diagnosing MS and dissecting for operation. Therefore, to avoid the complication associated with this special situation, the surgeons need to diagnose carefully and adopt an optimal treatment strategy. PMID:27445508

Mirizzi syndrome (MS) is a rare complication of chronic cholelithiasis, which is always caused by a calculus in the cystic duct or neck of the gallbladder, resulting in mechanical compression of common bileduct and the gallbladder. It is clinically characterized by abdominal pain, fever, as well as obstructive jaundice. During cholecystectomy, MS is seen as a dangerous adherent and inflammatory tissue in the area of Calot’s triangle. In the general population, aberrant right posterior hepatic duct, one of the causes of bileduct injury during duct surgery, is present in 4.8%–8.4% of people. Herein we report a rare case of a 76-year-old female patient, with hepatolithiasis of right posterior lobe and cholecysto-aberrant right posterior hepatic duct fistula. This is a special type of MS; however, interestingly, she did not have any symptoms, and the disease was found by physical examination incidentally. This case highlights another situation, namely, there may be difficulty in diagnosing MS and dissecting for operation. Therefore, to avoid the complication associated with this special situation, the surgeons need to diagnose carefully and adopt an optimal treatment strategy. PMID:27445508

The influence of pancreatic secretions on growth and brush-border enzyme activity, throughout the entire small intestine, was examined in the rat. Pancreatic secretions were excluded from the gut lumen by stapling the pancreatic ducts, without interruption of bile flow. The entire small intestine was studied as four segments; the duodenum and three distal segments of equal length. Weight of intestine and mucosa, and mucosal sucrase, isomaltase, lactase, and alkaline phosphatase activity were measured 10-15 days following pancreatic duct occlusion, or sham-operation. The duodenum of pancreatic duct-occluded animals exhibited significant hypertrophy. In general, specific and total disaccharidase activities were greater in duct-occluded animals than in controls throughout the intestine. The increase was more pronounced in distal than in proximal segments. The sucrase/isomaltase ratio was significantly greater in pancreatic duct-occluded animals than in controls in the two distal segments. Alkaline phosphatase activity was not affected by pancreatic duct occlusion. The greater relative increase of disaccharidase activities and sucrase/isomaltase activity ratios in the distal segments of duct-occluded animals, indicates a more important regulatory role of pancreatic enzymes in the distal small intestine. It is concluded that regulation of intestinal brush-border enzyme activity by pancreatic secretion is selective for enzyme and site as follows: disaccharidases, but not alkaline phosphatase, are regulated; the sucrase subunit of the sucrase/isomaltase complex is most sensitive to regulation, while lactase is least sensitive; and the regulatory effect on disaccharidases is greater in distal than in proximal intestine. PMID:3114740

Exposure to airborne particles is detrimental to human health and indoor exposures dominate total exposures for most people. The accidental or intentional release of aerosolized chemical and biological agents within or near a building can lead to exposures of building occupants to hazardous agents and costly building remediation. Particle deposition in heating, ventilation and air-conditioning (HVAC) systems may significantly influence exposures to particles indoors, diminish HVAC performance and lead to secondary pollutant release within buildings. This dissertation advances the understanding of particle behavior in HVAC systems and the fates of indoor particles by means of experiments and modeling. Laboratory experiments were conducted to quantify particle deposition rates in horizontal ventilation ducts using real HVAC materials. Particle deposition experiments were conducted in steel and internally insulated ducts at air speeds typically found in ventilation ducts, 2-9 m/s. Behaviors of monodisperse particles with diameters in the size range 1-16 {micro}m were investigated. Deposition rates were measured in straight ducts with a fully developed turbulent flow profile, straight ducts with a developing turbulent flow profile, in duct bends and at S-connector pieces located at duct junctions. In straight ducts with fully developed turbulence, experiments showed deposition rates to be highest at duct floors, intermediate at duct walls, and lowest at duct ceilings. Deposition rates to a given surface increased with an increase in particle size or air speed. Deposition was much higher in internally insulated ducts than in uninsulated steel ducts. In most cases, deposition in straight ducts with developing turbulence, in duct bends and at S-connectors at duct junctions was higher than in straight ducts with fully developed turbulence. Measured deposition rates were generally higher than predicted by published models. A model incorporating empirical equations based on

The CDUCT code utilizes a parabolic approximation to the convected Helmholtz equation in order to efficiently model acoustic propagation in acoustically treated, complex shaped ducts. The parabolic approximation solves one-way wave propagation with a marching method which neglects backwards reflected waves. The derivation of the parabolic approximation is presented. Several code validation cases are given. An acoustic lining design process for an example aft fan duct is discussed. It is noted that the method can efficiently model realistic three-dimension effects, acoustic lining, and flow within the computational capabilities of a typical computer workstation.

The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bileduct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

Anastomoses between the jejunum and the bileduct are an important component of many surgical procedures; however, risk factors for clinically relevant bile leaks have not yet been adequately defined. The objective of this study was to describe the incidence of bile leaks after hepaticojejunostomy and to define predictive factors associated with this risk and with surgical morbidity. Between October 2001 and April 2004, hepaticojejunostomies were performed in 519 patients in a standardized way. Patient- and treatment-related data were documented prospectively. A bile leak was defined as bilirubin concentration in the drains exceeding serum bilirubin with a consecutive change of clinical management or occurrence of a bilioma necessitating drainage. Surgical morbidity occurred in 15% of patients, the incidence of a bile leak was 5.6%. Multivariate analysis confirmed preoperative radiochemotherapy, preoperative low cholinesterase levels, biliary complications after liver transplantation necessitating a hepaticojejunostomy, and simultaneous liver resection as risk factors for bile leakages, whereas biliary complications after liver transplantation necessitating hepaticojejunostomy, simultaneous liver resection, and diabetes mellitus were significantly associated with postoperative surgical morbidity. Our results demonstrate that hepaticojejunostomy is a safe procedure if performed in a standardized fashion. The above found factors may help to better predict the risk for complications after hepaticojejunostomy. PMID:17394045

... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

Pancreatic development and the relationship of the islets with the pancreatic, hepatic, and bileducts were studied in the Nile tilapia, Oreochromis niloticus, from hatching to the onset of maturity at 7 months. The number of islets formed during development was counted, using either serial sections or dithizone staining of isolated islets. There was a general increase in islet number with both age and size. Tilapia housed in individual tanks grew more quickly and had more islets than siblings of the same age left in crowded conditions. The pancreas is a compact organ in early development, and at 1 day posthatch (dph) a single principal islet, positive for all hormones tested (insulin, SST-14, SST-28, glucagon, and PYY), is partially surrounded by exocrine pancreas. However, the exocrine pancreas becomes more disseminated in older fish, following blood vessels along the mesenteries and entering the liver to form a hepatopancreas. The epithelium of the pancreatic duct system from the intercalated ducts to the main duct entering the duodenum was positive for glucagon and SST-14 in 8 and 16 dph tilapia. Individual insulin-immunopositive cells were found in one specimen. At this early stage in development, therefore, the pancreatic duct epithelial cells appear to be pluripotent and may give rise to the small islets found near the pancreatic ducts in 16-37 dph tilapia. Glucagon, SST-14, and some PPY-positive enteroendocrine cells were present in the intestine of the 8 dph larva and in the first part of the intestine of the 16 dph juvenile. Glucagon and SST-14-positive inclusions were found in the apical cytoplasm of the mid-gut epithelium of the 16 dph tilapia. These hormones may have been absorbed from the gut lumen, since they are produced in both the pancreatic ducts and the enteroendocrine cells. At least three hepatic ducts join the cystic duct to form the bileduct, which runs alongside the pancreatic duct to the duodenum. PMID:15281064

The assessment of malignancies associated with anomalous union of the pancreaticobiliary duct (AUPBD) is essential for the design of appropriate treatment strategies. The aim of the present study is to measure the incidence of AUPBD-related pancreaticobiliary malignancy and to identify predictive factors. This retrospective cohort study included cases of 229 patients with AUPBD between January 1999 and December 2013. The impact of bileduct dilatation on the incidence of AUPBD-related pancreaticobiliary disease was measured, and predictive factors were evaluated.Among 229 patients with AUPBD, 152 had common bileduct dilatation (≥10 mm) (dilated group) and 77 did not (<10 mm) (nondilated group). Intrahepatic cholangiocarcinoma occurred more frequently in the nondilated group than in the dilated group (3.9% vs 0%; P bile duct were associated with occurrence of biliary tract cancers. In multivariate analysis, age ≥45 years (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.011-1.073, P bile duct dilatation. Age ≥45 years, P-C type, and biliary lipase level ≥45,000 IU/L are significantly associated with AUPBD-related biliary tract cancer. PMID:27196455

Abstract The assessment of malignancies associated with anomalous union of the pancreaticobiliary duct (AUPBD) is essential for the design of appropriate treatment strategies. The aim of the present study is to measure the incidence of AUPBD-related pancreaticobiliary malignancy and to identify predictive factors. This retrospective cohort study included cases of 229 patients with AUPBD between January 1999 and December 2013. The impact of bileduct dilatation on the incidence of AUPBD-related pancreaticobiliary disease was measured, and predictive factors were evaluated. Among 229 patients with AUPBD, 152 had common bileduct dilatation (≥10 mm) (dilated group) and 77 did not (<10 mm) (nondilated group). Intrahepatic cholangiocarcinoma occurred more frequently in the nondilated group than in the dilated group (3.9% vs 0%; P bile duct were associated with occurrence of biliary tract cancers. In multivariate analysis, age ≥45 years (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.011–1.073, P bile duct dilatation. Age ≥45 years, P-C type, and biliary lipase level ≥45,000 IU/L are significantly associated with AUPBD-related biliary tract cancer. PMID:27196455

SYNERGETICS, INC., has designed, developed, and tested an air handling duct system that integrates the air duct with the cornice trim of interior spaces. The device has the advantage that the normal thermal losses from ducts into unconditioned attics and crawl spaces can be totally eliminated by bringing the ducts internal to the conditioned space. The following report details work conducted in the second budget period to develop the Cornice Duct System into a viable product for use in a variety of residential or small commercial building settings. A full-scale prototype has been fabricated and tested in a laboratory test building at the Daylighting Facility at North Carolina State University., Based on the results of that testing, the prototype design as been refined, fabricated, installed, and extensively tested in a residential laboratory house. The testing indicates that the device gives substantially superior performance to a standard air distribution system in terms of energy performance and thermal comfort. Patent Number US 6,511,373 B2 has been granted on the version of the device installed and tested in the laboratory house. (A copy of that patent is attached.) Refinements to the device have been carried through two additional design iterations, with a particular focus on reducing installation time and cost and refining the air control system. These new designs have been fabricated and tested and show substantial promise. Based on these design and testing iterations, a final design is proposed as part of this document. That final design is the basis for a continuation in part currently being filed with the U.5, Patent office.

Summary Small molecule ligands that target to TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases. New insights into the mechanisms underlying the bariatric surgery and bile acid sequestrant treatment suggest that targeting the enterohepatic circulation to modulate gut-liver bile acid signaling, incretin production and microbiota represents a new strategy to treat obesity and type-2 diabetes. PMID:25584736

Bileduct mixed adenoneuroendocrine carcinoma (MANEC) is a rare entity. It is defined as having mixed elements of both neuroendocrine tumors (NET) and an adenocarcinoma element, the lesser component forming at least 30% of the tumor. It is a subtype of neuroendocrine carcinoma (NEC) showing both gland-forming epithelial tumor cells and neuroendocrine cells. It is generally misdiagnosed as cholangiocarcinoma on imaging studies. The preoperative pathological workup from the endoscopic retrograde cholangiography brush cytology usually misses the NET/NEC component since it often lies deeper in the tumor. However, it is reported that it is the NEC component that defines the prognosis of the tumor; hence, it is vital to identify the NEC component. We present a rare case of common hepatic duct (CHD) MANEC that was preoperatively misdiagnosed as cholangiocarcinoma. PMID:27375908

Bileduct mixed adenoneuroendocrine carcinoma (MANEC) is a rare entity. It is defined as having mixed elements of both neuroendocrine tumors (NET) and an adenocarcinoma element, the lesser component forming at least 30% of the tumor. It is a subtype of neuroendocrine carcinoma (NEC) showing both gland-forming epithelial tumor cells and neuroendocrine cells. It is generally misdiagnosed as cholangiocarcinoma on imaging studies. The preoperative pathological workup from the endoscopic retrograde cholangiography brush cytology usually misses the NET/NEC component since it often lies deeper in the tumor. However, it is reported that it is the NEC component that defines the prognosis of the tumor; hence, it is vital to identify the NEC component. We present a rare case of common hepatic duct (CHD) MANEC that was preoperatively misdiagnosed as cholangiocarcinoma. PMID:27375908

We report the successful management of acute cholecystitis using cystic duct stent placement in 3 patients with inoperable malignant cystic duct obstruction (2 cholangiocarcinoma and 1 pancreatic carcinoma). All patients underwent stent placement in the bileduct, using an uncovered stent in 2 and a covered stent in 1, to relieve jaundice occurring 8-184 days (mean 120 days) before the development of acute cholecystitis. The occluded cystic duct was traversed by a microcatheter and a stent was implanted 4-17 days (mean 12 days) after cholecystostomy. Acute cholecystitis was improved after the procedure in all patients. Two patients died 3 and 10 months later, while 1 has survived without cholecystitis for 22 months after the procedure to date.

We evaluated the efficacy of fatty-meal sonography for identifying patients with partial common duct obstruction. The test consisted of initial control measurements of common duct diameter followed by repeated measurements every 15 min for 60 min after a fatty meal consisting of Lipomul (1.5 ml/lb). The rationale proposed for the fatty-meal test is that in the presence of partial common duct obstruction, fat-induced increases in bile flow related to increased circulating levels of cholecystokinin are associated with an increase in the diameter of the common duct. Initial analysis of our data indicated that a change in diameter of +/- 1 mm was within the range of measurement error or possibly physiologic variation. In 44 control subjects (24 without a gallbladder), the common duct diameter either remained unchanged, showed an insignificant change of +/- 1 mm, or decreased (greater than or equal to 2 mm). The common duct diameter never showed an increase of more than 1 mm. The results of fatty-meal sonography in 47 patients with suspected partial common duct obstruction were negative in all 28 true-negative cases (specificity, 100%) and were positive (common duct increased by greater than or equal to 2 mm) in 14 of 19 true-positive cases (sensitivity, 74%). Thus, in this study a positive test finding always indicated partial common duct obstruction. Of the true-positive cases, fatty-meal sonography correctly identified seven of eight patients with cryptic obstructive sphincter-of-Oddi dysfunction (stenosis or dyskinesia) and five of nine patients with commun duct stones. We conclude that fatty-meal sonography is a useful noninvasive screening test for evaluating patients with suspected partial common duct obstruction. PMID:3287867

Bile salts are the major end-metabolites of cholesterol and are important in lipid digestion and shaping of the gut microflora. There have been limited studies of bile-salt variation in birds. The purpose of our study was to determine bile-salt variation among birds and relate this variation to current avian phylogenies and hypotheses on the evolution of bile salt pathways. We determined the biliary bile-salt composition of 405 phylogenetically diverse bird species, including 7 paleognath species. Bile salt profiles were generally stable within bird families. Complex bile-salt profiles were more common in omnivores and herbivores than in carnivores. The structural variation of bile salts in birds is extensive and comparable to that seen in surveys of bile salts in reptiles and mammals. Birds produce many of the bile salts found throughout nonavian vertebrates and some previously uncharacterized bile salts. One difference between birds and other vertebrates is extensive hydroxylation of carbon-16 of bile salts in bird species. Comparison of our data set of bird bile salts with that of other vertebrates, especially reptiles, allowed us to infer evolutionary changes in the bile salt synthetic pathway. PMID:21113274

Cystic dilatation within the lacrimal gland is thought to be related to chronic inflammation and scarring of the lacrimal gland ductules. We review the literature and discuss a case and of lacrimal duct cyst suppuration presenting with visual loss, external ophthalmoplegia, proptosis and ptosis. To our knowledge, only one other report of a lacrimal ductal cyst abscess has been reported in the literature so far. PMID:25208223

Aim of the study Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Method Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bileduct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Results Coptidis Rhizoma Aqueous Extract (CRAE), berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Conclusion Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis. PMID:23190573

A liquid-chromatographic technique with a post-column enzymatic reaction and fluorescence detection was validated for analysis of individual bile acids in the serum of rats. Extraction recoveries averaged 91.1% (SD 6.9%) for all bile acids. The assay was sensitive (minimum detection of 16.8 pmol per 100-microL injection), linear (r greater than 0.999 for concentrations ranging between 45 and 112,500 pmol per 100-microL injection), and reproducible (mean CVs for three different concentrations of standards and a serum pool ranged from 4.4% to 12.2%). In rats treated for three days with either neomycin, carbon tetrachloride, alpha-naphthylisothiocyanate, or total bile-duct ligation (five animals per group), total concentrations of bile acids were significantly increased (P less than 0.004). Concentrations of 16 of 17 individual bile acids differed significantly between groups (P less than 0.04). Examination of the relative concentrations (percent of total) of individual bile acids by canonical discriminant analysis placed each animal into the appropriate treatment or control group. Use of this technique in toxicological studies can help detect and identify specific types of disruptions in the enterohepatic circulation of bile acids. PMID:3665040

The average incidence of gallstones in european countries is about 25%. Excessive secretion of cholesterol into the bile can predispose to saturation and gallstone-formation. Obesity, overnutrition, diets rich in refined carbohydrates, diets high in cholesterol intake and poor in dietary fibre, lipid lowering drugs, age and female sex hormones are recognized causing increased cholesterol secretion into the bile. These metabolic consequences may predispose to a higher incidence of cholesterol gallstone than in normal persons. Taking all the results of the literature together patients with gallstones should be encouraged to take a low cholesterol, low calorie, low refined carbohydrate and high polyunsaturated fat diet rich in bran und vegetable fibre. Obese patients should reduce their body weight. These dietary recommendations should be given for patients with gallstones during bile acid therapy and after successful dissolution in order to prevent gallstone recurrence. PMID:3280933

Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bileduct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, the specific mechanisms by which bile acids may be acting to promote cholangiocarcinogenesis and invasive biliary tumor growth have not been fully established. Recent studies have shown that CBAs, but not free bile acids, stimulate CCA cell growth, and that an imbalance in the ratio of free to CBAs may play an important role in the tumorigenesis of CCA. Also, CBAs are able to activate extracellular signal-regulated kinase (ERK)1/2- and phosphatidylinositol-3-kinase/protein kinase B (AKT)-signaling pathways through sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes. In the current study, we demonstrate S1PR2 to be highly expressed in rat and human CCA cells, as well as in human CCA tissues. We further show that CBAs activate the ERK1/2- and AKT-signaling pathways and significantly stimulate CCA cell growth and invasion in vitro. Taurocholate (TCA)-mediated CCA cell proliferation, migration, and invasion were significantly inhibited by JTE-013, a chemical antagonist of S1PR2, or by lentiviral short hairpin RNA silencing of S1PR2. In a novel organotypic rat CCA coculture model, TCA was further found to significantly increase the growth of CCA cell spheroidal/“duct-like” structures, which was blocked by treatment with JTE-013. Conclusion: Our collective data support the hypothesis that CBAs promote CCA cell-invasive growth through S1PR2. PMID:24700501

Bile acids are potentially toxic end products of cholesterol metabolism and their concentrations must be tightly regulated. Homeostasis is maintained by both feed-forward regulation and feedback regulation. We used humanized transgenic mice incorporating 13 kb of the 5' regulatory flanking sequence of CYP3A4 linked to a lacZ reporter gene to explore the in vivo relationship between bile acids and physiological adaptive CYP3A gene regulation in acute cholestasis after bileduct ligation (BDL). Male transgenic mice were subjected to BDL or sham surgery prior to sacrifice on days 3, 6, and 10, and others were injected with intraperitoneal lithocholic acid (LCA) or vehicle alone. BDL resulted in marked hepatic activation of the CYP3A4/lacZ transgene in pericentral hepatocytes, with an 80-fold increase in transgene activation by day 10. Individual bile acids were quantified by liquid chromatography/mass spectrometry. Serum 6beta-hydroxylated bile acids were increased following BDL, confirming the physiological relevance of endogenous Cyp3a induction to bile acid detoxification. Although concentrations of conjugated primary bile acids increased after BDL, there was no increase in LCA, a putative PXR ligand, indicating that this cannot be the only endogenous bile acid mediating this protective response. Moreover, in LCA-treated animals, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining showed hepatic activation of the CYP3A4 transgene only on the liver capsular surface, and minimal parenchymal induction, despite significant liver injury. This study demonstrates that CYP3A up-regulation is a significant in vivo adaptive response to cholestasis. However, this up-regulation is not dependent on increases in circulating LCA and the role of other bile acids as regulatory molecules requires further exploration. PMID:14681232

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bileduct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. PMID:26505974

Bile salts are potent olfactory stimuli in fishes; however the biological functions driving such sensitivity remain poorly understood. We provide an integrative review of bile salts as semiochemicals in fish. First, we present characteristics of bile salt structure, metabolism, and function that are particularly relevant to chemical communication. Bile salts display a systematic pattern of structural variation across taxa, are efficiently synthesized, and are stable in the environment. Bile salts are released into the water via the intestine, urinary tract, or gills, and are highly water soluble. Second, we consider the potential role of bile salts as semiochemicals in the contexts of detecting nearby fish, foraging, assessing risk, migrating, and spawning. Lastly, we suggest future studies on bile salts as semiochemicals further characterize release into the environment, behavioral responses by receivers, and directly test the biological contexts underlying olfactory sensitivity.

Introduction Brunner's glands are submucosal glands found in the duodenum. Proliferation of these glands can lead to the formation of Brunner's gland hamartomas (BGHs), which are uncommon, asymptomatic and usually found incidentally. They are predominantly benign lesions, but instances of malignant transformation have been reported. Case History We describe a rare case in which a periampullary lesion was causing biliary obstruction on a background of weight loss, and was associated with dilatation of the common bileduct and pancreatic duct on computed tomography and magnetic resonance imaging. Further investigation with endoscopic ultrasound and biopsy did not provide a definitive diagnosis. Given the symptoms and findings upon investigations, we proceeded to pylorus-preserving pancreatoduodenectomy. Conclusions This was a rare case in which BGH gave rise to biliary obstruction against a background of weight loss. Due to a high index of suspicion (weight loss and evidence of dilatation of the common bileduct and pancreatic duct), this procedure was justified because the consequences of a missed periampullary cancer far outweighed surgical risks. PMID:27055413

PurposeThere have been few case reports describing cystic duct stent insertion in the management of acute cholecystitis secondary to benign disease with no case series published to date. We present our series demonstrating the role of cystic duct stents in managing benign gallbladder disease in those patients unfit for surgery.Materials and MethodsThirty three patients unfit for surgery in our institution underwent cystic duct stent insertion for the management of acute cholecystitis in the period June 2008 to June 2013. Patients underwent a mixture of transperitoneal and transhepatic gallbladder puncture. The cystic duct was cannulated with a hydrophilic guidewire which was subsequently passed through the common bileduct and into the duodenum. An 8Fr 12-cm double-pigtail stent was placed with the distal end lying within the duodenum and the proximal end within the gallbladder.ResultsTen patients presented with gallbladder perforation, 21 patients with acute cholecystitis, 1 with acute cholangitis and 1 with necrotising pancreatitis. The technical success rate was 91 %. We experienced a 13 % complication rate with 3 % mortality rate at 30 days.ConclusionCystic duct stent insertion can be successfully used to manage acute cholecystitis, gallbladder empyema or gallbladder perforations in those unfit for surgery and should be considered alongside external gallbladder drainage as a definitive mid-term treatment option.

Percutaneous cholecystostomy is well established as a temporising treatment option in selected patients presenting with acute cholecystitis. However, some patients who undergo cholecystostomy will have persistent discharge, which precludes catheter removal, or may not be medically suitable for future cholecystectomy. In these circumstances, percutaneous cystic duct stenting isa novel treatment option. It may delay or avoid the need for cholecystectomy, and thereby provide definitive treatment in a subset of patients who have acute cholecystitis and a high anaesthetic risk or limited life expectancy. Current application has been limited largely to patients with pre-existing malignant common bileduct strictures, but there is potential for the application to be broadened to include other subsets of patients. In this paper, we describe the technique used for percutaneous cystic duct stenting in a patient and report on its effectiveness. We also explore the technical considerations and consider the application of the procedure on other groups of patients. PMID:20976992

Dilation of the hex duct is an important factor in the operational lifetime of fuel subassemblies in liquid metal fast reactors. It is caused primarily by the irradiation-enhanced creep and void swelling of the hex duct material. Excessive dilation may jeopardize subassembly removal from the core or cause a subassembly storage problem where the grid size of the storage basket is limited. Dilation of the hex duct in Experimental Breeder Reactor II (EBR-II) limits useful lifetime because of these storage basket limitations. It is, therefore, important to understand the hex duct dilation behavior to guide the design and in-core management of fuel subassemblies in a way that excessive duct deformation can be avoided. To investigate the dilation phenomena, finite-element models of the hex duct have been developed. The inelastic analyses were performed using the structural analysis code, ANSYS. Both Type 316 and D9 austenitic stainless steel ducts are considered. The calculated dilations are in good agreement with profilometry measurements made after irradiation. The analysis indicates that subassembly interaction is an important parameter in addition to neutron fluence and temperature in determining hex duct dilation. 5 refs.

Roux-en-Y loop is considered the reconstruction method of choice in Orthotopic Liver Transplantation (OLT) for Primary Sclerosing Cholangitis (PSC). We have adopted an approach of duct-to-duct (D-D) reconstruction when recipient common bileduct is free of gross disease. Patients were divided into two groups: patients who underwent a Roux-en-Y choledochojejunostomy and patients who had a D-D anastomosis. Morbidity, mortality, disease recurrence and graft and patient survival were compared between the two groups and analyzed. Ninety-one patients had OLT for PSC. Sixty-three patients underwent a D-D biliary reconstruction, whereas 28 patients had a Roux-en-Y loop. Biliary leak complicated 8% from the D-D group, and 14% from the Roux-en-Y group (P = 0.08), whereas biliary strictures were identified in 10% vs. 7% patients from the D-D and Roux-en-Y group, respectively (P = 0.9). Actuarial 1, 3 and 10 year survival for D-D and Roux-en-Y group was (87%, 80% and 62%) and (82%, 73% and 73%), respectively (P = 0.7). The corresponding 1, 3 and 10 year graft survival was (72%, 58% and 42%) and (67%, 58% and 53%), respectively (P = 0.6). No difference was seen in disease recurrence rates. D-D biliary reconstruction in OLT for selected PSC patients remains our first option of reconstruction. PMID:22017643

Hepaticojejunostomy is an important part of many surgical procedures including pancreaticoduodenectomy. Biliary leakage from hepaticojejunostomy may be associated with intraabdominal abscess formation, biliary peritonitis, and even mortality. A 72-year-old female patient was admitted to our hospital with obstructive jaundice. After initial evaluation, she was diagnosed with distal common bileduct obstruction without accurate diagnosis. Before planned pancreaticoduodenectomy, biliary drainage with a T-tube was performed due to the presence of cholangitis. After the first operation, pancreaticoduodenectomy was performed. Postinflammatory changes around the hilar region made the hepaticojejunostomy risky. A bilio-digestive anastomosis was performed using a new technique. A nasogastric tube was placed into the common bileduct proximal to the anastomosis. The postoperative course of the patient was uneventful. The use of a nasogastric tube as a stent in risky hepaticojejunostomies is a simple technique that can be beneficial. PMID:27212998

Hepaticojejunostomy is an important part of many surgical procedures including pancreaticoduodenectomy. Biliary leakage from hepaticojejunostomy may be associated with intraabdominal abscess formation, biliary peritonitis, and even mortality. A 72-year-old female patient was admitted to our hospital with obstructive jaundice. After initial evaluation, she was diagnosed with distal common bileduct obstruction without accurate diagnosis. Before planned pancreaticoduodenectomy, biliary drainage with a T-tube was performed due to the presence of cholangitis. After the first operation, pancreaticoduodenectomy was performed. Postinflammatory changes around the hilar region made the hepaticojejunostomy risky. A bilio-digestive anastomosis was performed using a new technique. A nasogastric tube was placed into the common bileduct proximal to the anastomosis. The postoperative course of the patient was uneventful. The use of a nasogastric tube as a stent in risky hepaticojejunostomies is a simple technique that can be beneficial. PMID:27212998

The objective was to demonstrate the cost and weight advantages that could be obtained by utilizing the graphite/PMR15 material system to replace titanium in selected turbofan engine applications. The first component to be selected as a basis for evaluation was the outer bypass duct of the General Electric F404 engine. The operating environment of this duct was defined and then an extensive mechanical and physical property test program was conducted using material made by processing techniques which were also established by this program. Based on these properties, design concepts to fabricate a composite version of the duct were established and two complete ducts fabricated. One of these ducts was proof pressure tested and then run successfully on a factory test engine for over 1900 hours. The second duct was static tested to 210 percent design limit load without failure. An improved design was then developed which utilized integral composite end flanges. A complete duct was fabricated and successfully proof pressure tested. The net results of this effort showed that a composite version of the outer duct would be 14 percent lighter and 30 percent less expensive that the titanium duct. The other type of structure chosen for investigation was the F404 fan stator assembly, including the fan stator vanes. It was concluded that it was feasible to utilize composite materials for this type structure but that the requirements imposed by replacing an existing metal design resulted in an inefficient composite design. It was concluded that if composites were to be effectively used in this type structure, the design must be tailored for composite application from the outset.

In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic pathways. Signaling via these pathways will vary depending on the tissue and the concentration and chemical structure of the bile acid species. Important determinants of the size and composition of the bile acid pool are their efficient enterohepatic recirculation, their host and microbial metabolism, and the homeostatic feedback mechanisms connecting hepatocytes, enterocytes, and the luminal microbiota. This review focuses on the mammalian intestine, discussing the physiology of bile acid transport, the metabolism of bile acids in the gut, and new developments in our understanding of how intestinal metabolism, particularly by the gut microbiota, affects bile acid signaling. PMID:25210150

Turbine systems are provided. A turbine system includes a transition duct comprising an inlet, an outlet, and a duct passage extending between the inlet and the outlet and defining a longitudinal axis, a radial axis, and a tangential axis. The outlet of the transition duct is offset from the inlet along the longitudinal axis and the tangential axis. The duct passage includes an upstream portion and a downstream portion. The upstream portion extends from the inlet between an inlet end and an aft end. The downstream portion extends from the outlet between an outlet end and a head end. The turbine system further includes a joint coupling the aft end of the upstream portion and the head end of the downstream portion together. The joint is configured to allow movement of the upstream portion and the downstream portion relative to each other about or along at least one axis.

The reflection coefficients and inertial end corrections of several duct terminations, including finite length duct extensions perpendicular to an infinite wall, as well as at a number of angles, curved interface surfaces, and annular cavities, are determined and analyzed in the absence of flow by employing the boundary element method. Predictions for the classical unflanged and flanged circular ducts show good agreement with analytical and computational results available in the literature. The predictions for curved interface surfaces (bellmouth or horn) are also consistent with the available experimental data. In view of its high reflection coefficient, the duct termination with an annular cavity may be suggested for the suppression of noise radiation in a specific frequency band or for an effective wave reflection from the termination. PMID:11325101

The linearized equations describing the propagation of sound in variable area ducts containing flow are shown to be singular when the duct mean flow is sonic. The singularity is removed when previously ignored nonlinear terms are retained. The results of a numerical study, for the case of plane waves propagating in a one-dimensional converging-diverging duct, show that the sound field is adequately described by the linearized equations only when the axial mean flow Mach number at the duct throat M sub th 0.6. For M sub th 0.6, the numerical results showed that acoustic energy flux was not conserved. An attempt was made to extend the study to include the nonlinear behavior of the sound field. Meaningful results were not obtained due, primarily, to numerical difficulties.

Improved liquid sodium flow ducts for nuclear reactors are described wherein the improvement comprises varying the wall thickness of each of the walls of a polygonal tubular duct structure so that each of the walls is of reduced cross-section along the longitudinal center line and of a greater cross-section along wall junctions with the other walls to form the polygonal tubular configuration.

Two variations on the tests for duct leakage currently embodied in ASHRAE Standard 152P (Method of Test for Determining the Design and Seasonal Efficiencies of Residential Thermal Distribution Systems) are presented. Procedures are derived for calculating supply and return duct leakage to/from outside using these new variations. Results of these tests are compared with the original ones in Standard 152P on the basis of data collected in three New York State homes.

Two variations on the tests for duct leakage currently embodied in ASHRAE Standard 152P (Method of Test for Determining the Design and Seasonal Efficiencies of Residential Thermal Distribution Systems) are presented. Procedures are derived for calculating supply and return duct leakage to/from outside using these new variations. Results of these tests are compared with the original ones in Standard 152P on the basis of data collected in three New York State homes.

Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

Suppressions due to acoustic treatment in the annular exhaust duct of a model fan were theoretically predicted and compared with measured suppressions. The predictions are based on the modal analysis of sound propagation in a straight annular flow duct with segmented treatment. Modal distributions of the fan noise source (fan-stator interaction only) were measured using in-duct modal probes. The flow profiles were also measured in the vicinity of the modal probes. The acoustic impedance of the single degree of freedom treatment was measured in the presence of grazing flow. The measured values of mode distribution of the fan noise source, the flow velocity profile and the acoustic impedance of the treatment in the duct were used as input to the prediction program. The predicted suppressions, under the assumption of uniform flow in the duct, compared well with the suppressions measured in the duct for all test conditions. The interaction modes generated by the rotor-stator interaction spanned a cut-off ratio range from nearly 1 to 7.

Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe](-). Previous work has definitively demonstrated the presence of [(GS)2AsSe](-) in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe](-). Since rats have no gall bladder, the bile proceeds directly through the bileduct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe](-), with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations. PMID:26883676

Cholesterol crystallization is a key step in gallstone formation and is influenced by numerous factors. Human bile contains various bile salts having different hydrophobicity and micelle-forming capacities, but the importance of lipid composition to bile metastability remains unclear. This study investigated the effect of bile salts on cholesterol crystallization in model bile (MB) systems. Supersaturated MB systems were prepared with an identical composition on a molar basis (taurocholate/phosphatidylcholine/cholesterol, 152 mM:38 mM: 24 mM), except for partial replacement of taurocholate (10, 20, and 30%) with various taurine-conjugated bile salts. Cholesterol crystallization was quantitatively estimated by spectrophotometrically measuring crystal-related turbidity and morphologically scanned by video-enhanced microscopy. After partial replacement of taurocholate with hydrophobic bile salts, cholesterol crystallization increased dose-dependently without changing the size of vesicles or crystal morphology and the rank order of crystallization was deoxycholate>chenodeoxycholate>cholate (control MB). All of the hydrophilic bile salts (ursodeoxycholate, ursocholate and beta-muricholate) inhibited cholesterol precipitation by forming a stable liquid-crystal phase, and there were no significant differences among the hydrophilic bile-salt species. Cholesterol crystallization was markedly altered by partial replacement of bile salts with a different hydrophobicity. Thus minimal changes in bile-salt composition may dramatically alter bile lipid metastability. PMID:10333488

Circadian control of nutrient availability is critical to efficiently meet the energetic demands of an organism. Production of bile acids (BAs), which facilitate digestion and absorption of nutrients, is a major regulator of this process. Here we identify a KLF15-Fgf15 signalling axis that regulates circadian BA production. Systemic Klf15 deficiency disrupted circadian expression of key BA synthetic enzymes, tissue BA levels and triglyceride/cholesterol absorption. Studies in liver-specific Klf15-knockout mice suggested a non-hepatic basis for regulation of BA production. Ileal Fgf15 is a potent inhibitor of BA synthesis. Using a combination of biochemical, molecular and functional assays (including ileectomy and bileduct catheterization), we identify KLF15 as the first endogenous negative regulator of circadian Fgf15 expression. Elucidation of this novel pathway controlling circadian BA production has important implications for physiologic control of nutrient availability and metabolic homeostasis. PMID:26040986

The intrahepatic biliary ducts transport bile produced by the hepatocytes out of the liver. Defects in biliary cell differentiation and biliary duct remodeling cause a variety of congenital diseases including Alagille Syndrome and polycystic liver disease. While the molecular pathways regulating biliary cell differentiation have received increasing attention (Lemaigre, 2010), less is known about the cellular behavior underlying biliary duct remodeling. Here, we have identified a novel gene, claudin 15-like b (cldn15lb), which exhibits a unique and dynamic expression pattern in the hepatocytes and biliary epithelial cells in zebrafish. Claudins are tight junction proteins that have been implicated in maintaining epithelial polarity, regulating paracellular transport, and providing barrier function. In zebrafish cldn15lb mutant livers, tight junctions are observed between hepatocytes, but these cells show polarization defects as well as canalicular malformations. Furthermore, cldn15lb mutants show abnormalities in biliary duct morphogenesis whereby biliary epithelial cells remain clustered together and form a disorganized network. Our data suggest that Cldn15lb plays an important role in the remodeling process during biliary duct morphogenesis. Thus, cldn15lb mutants provide a novel in vivo model to study the role of tight junction proteins in the remodeling of the biliary network and hereditary cholestasis. PMID:22020048

The bile salts present in gallbladder bile of the West Indian manatee, Trichechus manatus latirostris, an herbivorous marine mammal of the tropical and subtropical margins of the Atlantic Ocean, were found to consist of a mixture of bile alcohol sulfates. Bile acids, previously believed to be present in all mammals, were not detected. Using chromatography, mass spectrometry, and 1H- and 13C-nuclear magnetic resonance spectroscopy, the major bile alcohol was identified as 5 beta-cholestane-3 alpha,6 beta,7 alpha-25,26-pentol; that is, it had the nuclear structure of alpha-muricholic acid and the side chain structure of bufol. This compound has not been described previously and the trivial name "alpha-trichechol" is proposed. The second most abundant compound was 5 beta-cholestane-3 alpha,7 alpha,25,26-tetrol. Other bile alcohols were tentatively identified as 5 beta-cholestane-3 alpha,6 beta,7 beta,25,26-pentol (named beta-trichechol), 3 alpha,6 alpha,7 beta, 25-26-pentol (named omega-trichechol) and 5 beta-cholestane-3 alpha,6 beta,7 alpha,26-tetrol. The 1H and 13C NMR spectra of the four 6,7 epimers of 3,6,7 trihydroxy bile acids are described and discussed. All bile alcohols were present as ester sulfates, the sulfate group being tentatively assigned to the 26-hydroxy group. 12-Hydroxy compounds were not detected. The manatee is the first mammal found to lack bile acids, presumably because it lacks the enzymes required for oxidation of the 26-hydroxy group to a carboxylic acid. Trichechols, like other bile salts, are water-soluble end products of cholesterol metabolism; whether they also function as biological surfactants in promoting biliary cholesterol secretion or lipid digestion is unknown. PMID:3392467

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics. PMID:19490986

The development and validation of a direct method for measuring maximum cholesterol solubility in bile is described. Application of this method to five large mammalian species, including man, produced a micellar zone significantly smaller than that previously reported. Further studies on in vitro model solutions patterned after bile confirmed this new micellar zone. Thus, direct evidence demonstrates that the micellar zone boundary derived in vitro from model solutions is applicable to human gallbladder bile. Using the present criteria, normal human bile, in contrast to bile from other mammalian species, is commonly supersaturated with cholesterol. A male-female difference in bile composition is not demonstrable despite the well-established female preponderance of cholelithiasis. Bile from patients with cholesterol cholelithiasis has a micellar zone similar to normals but differs compositionally in that there is a greater excess of cholesterol above saturation. We conclude that cholesterol supersaturation may be a necessary but not solely sufficient cause for gallstone formation. PMID:4703231

Bile acids are potentially toxic compounds and their levels of hepatic production, uptake, and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. Both restricted feedi...

The sulphation of bile acids is an important pathway for the detoxification and elimination of bile acids during cholestatic liver disease. A dehydroepiandrosterone (DHEA) sulphotransferase has been purified from male and female human liver cytosol using DEAE-Sepharose CL-6B and adenosine 3',5'-diphosphate-agarose affinity chromatography [Falany, Vazquez & Kalb (1989) Biochem. J. 260, 641-646]. Results in the present paper show that the DHEA sulphotransferase, purified to homogeneity, is also reactive towards bile acids, including lithocholic acid and 6-hydroxylated bile acids, as well as 3-hydroxylated short-chain bile acids. The highest activity towards bile acids was observed with lithocholic acid (54.3 +/- 3.6 nmol/min per mg of protein); of the substrates tested, the lowest activity was detected with hyodeoxycholic acid (4.2 +/- 0.01 nmol/min per mg of protein). The apparent Km values for the enzyme are 1.5 +/- 0.31 microM for lithocholic acid and 4.2 +/- 0.73 microM for taurolithocholic acid. Lithocholic acid also competitively inhibits DHEA sulphation by the purified sulphotransferase (Ki 1.4 microM). No evidence was found for the formation of bile acid sulphates by sulphotransferases different from the DHEA sulphotransferase during purification work. The above results suggest that a single steroid sulphotransferase with broad specificity encompassing neutral steroids and bile acids exists in human liver. PMID:2268288

Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis. PMID:26587777

Radiation-induced bowel disease manifested by debilitating diarrhea is an unfortunate consequence of therapeutic irradiation for pelvic malignancies. Although the mechanism for this diarrhea is not well understood, many believe it is the result of damage to small bowel mucosa and subsequent bile acid malabsorption. Excess amounts of bile acids, especially the dihydroxy components, are known to induce water and electrolyte secretion and increase bowel motility. We have directly measured individual and total bile acids in the stool samples of 11 patients with radiation-induced diarrhea and have found bile acids elevated two to six times normal in eight of them. Our patients with diarrhea and increased bile acids in their stools had prompt improvement when given cholestyramine. They had fewer stools and returned to a more normal life-style.

Oral cholelitholytic bile acid therapy has become established treatment for selected patients with cholesterol gallstones. The treatment finds its clinical application both alone and in combination with ESWL. UDCA alone or, less commonly, a combination of this bile acid with CDCA is used. Optimal results can be expected only in carefully selected patients. Bile acid dissolution therapy is most successful in patients with radiolucent gallstones which are < or = 0.5 cm in diameter or are shown by OCG to be floating. Dissolution is seldom seen when the stones are > 1 cm in size. Cholelitholytic treatment in combination with ESWL yields optimal results in single radiolucent gallstones which are not greater than 2 cm. ESWL thus makes it possible to use medical treatment effectively in single 1-2 cm gallstones when bile acids alone would not be successful. Bile acid treatment is extremely safe, especially if UDCA is given without the addition of CDCA. PMID:1486209

To characterize the transport mechanisms responsible for formation of canalicular bile, we have examined the effects of ion substitution on bile acid-dependent and bile acid-independent bile formation by the isolated perfused rat liver. Complete replacement of perfusate sodium with choline and lithium abolished taurocholate-induced choleresis and reduced biliary taurocholate output by greater than 70%. Partial replacement of perfusate sodium (25 of 128 mM) by choline reduced bile acid-independent bile formation by 30% and replacement of the remaining sodium (103 mM) by choline reduced bile acid-independent bile formation by an additional 64%. In contrast, replacement of the remaining sodium (103 mM) by lithium reduced bile acid-independent bile formation by only an additional 20%, while complete replacement of sodium (128 mM) by lithium reduced bile formation by only 17%, and lithium replaced sodium as the predominant biliary cation. Replacement of perfusate bicarbonate by Tricine, a zwitterionic amino acid buffer, decreased bile acid-independent bile formation by greater than or equal to 50% and decreased biliary bicarbonate output by approximately 60%, regardless of the accompanying cation. In separate experiments, replacement of sodium by lithium essentially abolished Na,K-ATPase activity measured either as ouabain-suppressible ATP hydrolysis in rat liver or kidney homogenates, or as ouabain-suppressible 86Rb uptake by cultured rat hepatocytes. These studies indicate that bile acid(taurocholate)-dependent bile formation by rat liver exhibits a specific requirement for sodium, a finding probably attributable to the role(s) of sodium in hepatic sodium-coupled taurocholate uptake and/or in maintenance of Na,K-ATPase activity. The surprising finding that bile acid-independent bile formation was substantially unaltered by complete replacement of sodium with the permeant cation lithium does not appear to be explained by Na,K-ATPase-mediated lithium transport. Although

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonize our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesized in the liver from cholesterol. Host enzymes conjugate the newly synthesized free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilization of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile. PMID:24399996

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonize our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesized in the liver from cholesterol. Host enzymes conjugate the newly synthesized free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilization of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile. PMID:24399996

The Evaporation Duct Communication (EDCOM) project is an effort to provide an alternative ship-to-ship communications channel using the natural environment. A microwave communication link can be used on an over-the-water, over-the-horizon path through the evaporation duct. This report shows how a microwave communication link, operating at a range separation of more than twice the line-of-sight range, can be constructed. This link can achieve about 80-percent availability at a transmission frequency of 14.5 GHz and can be constructed using off-the-shelf RF equipment. Operation of this link will provide the first set of measurements of channel capacity that can be critically dependent on the existence of an oceanic evaporation duct. Construction of this link presents a unique opportunity to study and evaluate an alternative communications channel that can be used to alleviate naval battlegroup communications load.

Cholestasis results when excretion of bile acids from the liver is interrupted. Liver injury occurs during cholestasis, and recent studies showed that inflammation is required for injury. Our previous studies demonstrated that early growth response factor-1 (Egr-1) is required for development of inflammation in liver during cholestasis, and that bile acids upregulate Egr-1 in hepatocytes. What remains unclear is the mechanism by which bile acids upregulate Egr-1. Bile acids modulate gene expression in hepatocytes by activating the farnesoid X receptor (FXR) and through activation of mitogen-activated protein kinase (MAPK) signaling. Accordingly, the hypothesis was tested that bile acids upregulate Egr-1 in hepatocytes by FXR and/or MAPK-dependent mechanisms. Deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) stimulated upregulation of Egr-1 to the same extent in hepatocytes isolated from wild-type mice and FXR knockout mice. Similarly, upregulation of Egr-1 in the livers of bileduct-ligated (BDL) wild-type and FXR knockout mice was not different. Upregulation of Egr-1 in hepatocytes by DCA and CDCA was prevented by the MEK inhibitors U0126 and SL-327. Furthermore, pretreatment of mice with U0126 prevented upregulation of Egr-1 in the liver after BDL. Results from these studies demonstrate that activation of MAPK signaling is required for upregulation of Egr-1 by bile acids in hepatocytes and for upregulation of Egr-1 in the liver during cholestasis. These studies suggest that inhibition of MAPK signaling may be a novel therapy to prevent upregulation of Egr-1 in liver during cholestasis.

This is a case report of a three-month-old male who presented to clinic with a cystic lesion under the tongue. On clinical examination, a cystic lesion was observed in the, floor-of-mouth. The patient was referred to Paediatric Otorhinolaryngology service for further management. The differential diagnoses for floor-of-mouth lesions should be reviewed with primary focus on the Wharton's duct atresia and its management. It is crucial to recognize submandibular duct atresia in the primary Paediatric clinic in order to expedite management of lesion before complications arise including infection, enlargement of cyst, and feeding and breathing difficulties. PMID:27042492

Formation of bile requires the coordinated function of two epithelial cell types: hepatocytes, that are responsible for secretion of the major osmolytes and biliary constituents and cholangiocytes that regulate the fluidity and alkalinity of bile through secretion of osmolytes such as Cl- and HCO3- Studies in isolated cholangiocyte preparations have elucidated the basic transport mechanisms involved in constitutive and stimulated secretory activities in the biliary epithelium. Basolateral Na+/H+ exchanger and Na+:HCO3- symporter mediate HCO3- uptake, while an apical cAMP-activated Cl-/HCO3- exchanger secretes bicarbonate into the lumen. Cholangiocytes also possess a cAMP-stimulated Cl- conductance (CFTR) and a Ca-activated Cl- channel, both likely located at the apical membrane. Cholangiocyte secretory functions are regulated by a complex network of hormones mainly acting via the cAMP system. In addition, recent data indicate that part of the regulation of ductular secretion may take place at the apical membrane of the cholangiocyte through factors present into the bile, such as ATP, bile acids and glutathione. Primary damage to the biliary epithelium is the cause of several chronic cholestatic disorders (cholangiopathies). From a pathophysiological point of view, common to all cholangiopathies is the coexistance of cholangiocyte death and proliferation and various degrees of portal inflammation and fibrosis. Cholestasis dominates the clinical picture and, pathophysiologically, may initiate or worsen the process. Alterations in biliary electrolyte transport could contribute to the pathogenesis of cholestasis in primary bileduct diseases. Cystic Fibrosis-related liver disease represents an example of biliary cirrhosis secondary to a derangement of cholangiocyte ion transport. Most primary cholangiopaties recognize an immune-mediated pathogenesis. Cytokines, chemokines, and proinflammatory mediators released in the portal spaces or produced by the cholangiocyte

Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules. PMID:24080386

Spontaneous extrahepatic bileduct perforation is generally seen in infants. Although rarely seen in adults, it may be seen with fatal bile peritonitis. Therefore, for a patient presenting with acute abdominal symptoms, differential diagnosis must be made with radiological imaging such as abdominal ultrasonography or computed tomography, without any loss of time. In these imaging tests, in cases of gallstone disease together with perihepatic free fluid or choledocus which can not be monitored, it should be considered in the differential diagnosis. An emergency surgical intervention should be planned to avoid serious complications. The aim of this paper was to present the rare cause of acute abdomen which developed associated with spontaneous common hepatic canal perforation in an adult. PMID:27135087

Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities for their potential to cause liver injury. We examined the serum biochemistry, liver histopathology, and bile acid profiles by LC-MS/MS, and the mRNA expression of transporters and CYPs by an RT-PCR after the following treatments to male Crl:CD (SD) rats: (a) bileduct ligation (BDL); (b) a single oral dose of 150 mg/kg α-naphthylisothiocyanate (ANIT); and (c) repeated oral doses of a novel pyrrolidinecarboxylic acid derivative (abbreviated as PCA) at 30, 300, and 1000 mg/kg. The serum total bile acid levels and bilirubin concentrations were found to be elevated in all of the groups. However, the bile acid component profiles of the PCA group differed significantly from BDL and ANIT models: deoxycholic acid, lithocholic acid, and sulfated bile acids were upregulated in a dose-dependent manner only in the PCA group. In addition, the PCA group demonstrated high levels of hepatic heme oxygenase-1 expression, whereas the profiles of the mRNA levels of the hepatic transporters and CYPs of all groups were found to be similar. The histopathological findings, for both the BDL and ANIT groups, were of bileduct hyperplasia, hepatocyte degeneration and necrosis. In contrast, only bileduct hyperplasia and hepatocyte degeneration were observed in the PCA group, even at a lethal dose. These results indicated that PCA induced a cholestatic condition and the increase of oxidative stress markers implies that this will also lead hepatocellular injury. In conclusion, the serum bile acid components and sulfated bile acid levels, and the expression of oxidative stress markers could provide information that aids in the diagnosis of liver injury type and helps to elucidate the mechanisms of hepatotoxicity. These findings can be extrapolated into our clinical investigation. The analysis of these crucial biomarkers is likely to be a useful screening tool in the lead

Selective peptide cleavage has provided a general procedure for the study of the structure, including stereochemistry, of plant bile pigments. The information derived from the synthesis and spectral analysis of a series of 2,3-dihydrodioxobilins allows the determination of the trans relative stereochemistry for ring A of the ..beta../sub 1/-phycocyanobilin from C-phycocyanin as well as for ring A of phytochrome. A complete structure proof of the five phycoerythrobilins attached to the ..cap alpha.. and ..beta.. subunits of B-phycoerythrin is described. One of these tetrapyrroles is doubly-peptide linked to a single peptide chain through two thioethers at the C-3' and C-18' positions. The four remaining phycoerythrobilins are singly-linked to the protein through thioethers at the C-3' position and all possess the probable stereochemistry C-2(R), C-3(R), C-3'(R), and C-16(R).

Studies of hepatic bile formation reported in 1958 established that it was an osmotically generated water flow. Intravenous infusion of sodium taurocholate established a high correlation between hepatic bile flow and bile acid excretion. Secretin, a hormone that stimulates bicarbonate secretion, was also found to increase hepatic bile flow. The…

Background: Vitellointestinal duct (VID) or omphalomesenteric duct anomalies are secondary to the persistence of the embryonic vitelline duct, which normally obliterates by weeks 5–9 of intrauterine life. Methods: This is a retrospective analysis of a total of 16 patients of symptomatic remnants of vitellointestinal duct from period of Jan 2009 to May 2013. Results: Male to female ratio (M:F) was 4.3:1 and mean age of presentation was 2 months and their mode of presentation was: patent VID in 9 (56.25%) patients, umbilical cyst in 2(12.25%), umbilical granuloma in 2 (12.25%), and Meckel diverticulum as content of hernia sac in obstructed umbilical hernia in 1 (6.25%) patient. Two patients with umbilical fistula had severe electrolyte disturbance and died without surgical intervention. Conclusion: Persistent VID may have varied presentations in infancy. High output umbilical fistula and excessive bowel prolapse demand urgent surgical intervention to avoid morbidity and mortality. PMID:27433448

The procedure for designing acoustic treatment panels used to line the walls of aircraft engine ducts and for estimating the resulting suppression of turbofan engine duct noise is discussed. This procedure is intended to be used for estimating noise suppression of existing designs or for designing new acoustic treatment panels and duct configurations to achieve desired suppression levels.

... requirements relative to the passage of smoke and flame as the fire control boundary penetrated; (2) A steel duct penetrating an A-Class fire control boundary must be of at least 11 USSG, and a steel duct... duct penetrating an A-Class fire control boundary and opening into a space formed by that boundary...

... requirements relative to the passage of smoke and flame as the fire control boundary penetrated; (2) A steel duct penetrating an A-Class fire control boundary must be of at least 11 USSG, and a steel duct... duct penetrating an A-Class fire control boundary and opening into a space formed by that boundary...

Bile acids have been traditionally thought of as having an important role in fat emulsification. It is now emerging that they act as important signalling molecules that not only autoregulate their own synthesis but also influence lipid and glucose metabolism. Although, the mechanisms that underlie the regulation of bile acid homeostasis have been well characterised in normal physiology, the impact of pregnancy on bile acid regulation is still poorly understood. This review summarises the main regulatory mechanisms underlying bile acid homeostasis and discusses how pregnancy, a unique physiological state, can modify them. The fetoplacental adaptations that protect against fetal bile acid toxicity are reviewed. We highlight the importance of bile acid regulation during gestation by discussing the liver disease of pregnancy, intrahepatic cholestasis of pregnancy (ICP) and how genetic, endocrine and environmental factors contribute to the disease aetiology at a cellular and molecular level. PMID:23159988

AIM: To further reduce the risk of bleeding or bile leakage. METHODS: We performed endoscopic ultrasound guided biliary drainage in 6 patients in whom endoscopic retrograde cholangiopancreatography (ERCP) had failed. Biliary access of a dilated segment 2 or 3 duct was achieved from the stomach using a 19G needle. After radiologically confirming access a guide wire was placed, a transhepatic tract created using a 6 Fr cystotome followed by balloon dilation of the stricture and antegrade metallic stent placement across the malignant obstruction. This was followed by placement of an endocoil in the transhepatic tract. RESULTS: Dilated segmental ducts were observed in all patients with the linear endoscopic ultrasound scope from the proximal stomach. Transgastric biliary access was obtained using a 19G needle in all patients. Biliary drainage was achieved in all patients. Placement of an endocoil was possible in 5/6 patients. All patients responded to biliary drainage and no complications occurred. CONCLUSION: We show that placing endocoils at the time of endoscopic ultrasound guided biliary stenting is feasible and may reduce the risk of bleeding or bile leakage. PMID:23678378

The effect of different concentrations of oxen bile and individual bile acids or their sodium salts on the gastric mucosa of rats was investigated in combination with immobilization stress. A statistically significant higher frequency of ulcers was only determined in the application of 10% oxen bile. Dosages on 10% sodium glycocholic acid demonstrated strong toxic damage with atonic dilation of the stomach and extensive mucosal bleeding.

This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5), farnesoid X receptor (FXR), ursodeoxycholic acid (UDCA) and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5–7 years) regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events. PMID:26579437

Limy bile is a relatively rare condition, in which a radiopaque material is visible in the gallbladder on plain radiography or computerized tomography. Cases of complicated hyperparathyroidism are extremely rare. We report a patient with right upper quadrant and epigastric pain and extremity weakness in whom abdominal tomography showed limy bile in the gallbladder and laboratory values showed high levels of serum calcium and parathormone. PMID:25821626

Von Meyenburg complexes (VMC) are a cluster of benign liver malformations including biliary cystic lesions, with congenital fibrocollagenous stroma. This rare entity can mimick multiple secondary hepatic lesions. We report a case of a 56-year-old woman who had multiples liver lesions 12 years after operation for breast cancer. Biopsy of the hepatic lesion confirmed the diagnosis of VMC. Preoperative discovery of multiple gray-white nodular lesions scattered on the surface of the liver should not always contraindicate curative liver resection. The diagnosis of VMC should be known and confirmed with liver biopsy. PMID:21103275

Von Meyenburg complexes (VMC) are a cluster of benign liver malformations including biliary cystic lesions, with congenital fibrocollagenous stroma. This rare entity can mimick multiple secondary hepatic lesions. We report a case of a 56-year-old woman who had multiples liver lesions 12 years after operation for breast cancer. Biopsy of the hepatic lesion confirmed the diagnosis of VMC. Preoperative discovery of multiple gray-white nodular lesions scattered on the surface of the liver should not always contraindicate curative liver resection. The diagnosis of VMC should be known and confirmed with liver biopsy. PMID:21103275

A serum-free, feeder-cell-dependent, selective culture system for the long-term culture of porcine hepatocytes or cholangiocytes was developed. Liver cells were isolated from 1 wk old pigs or young adult pigs (25 and 63 kg live weight) and were placed in primary culture on feeder-cell layers of mit...

Although percutaneous transhepatic biliary drainage (PTBD) and tract dilatation (TD) are very painful procedures, almost all of those procedures have been conducted under local anesthesia and opioid injection due to the lack of manpower and time. Celiac plexus block (CPB) is an interventional technique used for diagnostic and therapeutic purposes in the treatment of abdominovisceral pain. CPB decreases the side effects of opioid medications and enhances analgesia from medications. We present the case of a patient who underwent PTBD and TD under CPB in order to reduce procedure-related abdominal pain.CPB can be a useful alternative technique for pain management during and after biliary interventional procedures, although CPB-induced complications must always be kept in mind. PMID:27399112

Biliary tract cancer or extrahepatic cholangiocarcinoma (ECCA) represents the sixth commonest cause of cancer in the gastrointestinal tract in western countries. We aimed to characterize the microbiota and its predicted associated functions in the biliary tract of ECCA and benign biliary pathology (BBP). Samples were taken from 100 patients with ECCA and 100 patients with BBP by endoscopic cholangio-pancreatography for DNA extraction. Ten patients with ECCA and ten with BBP were selected for microbiota studies using the V4-16S rRNA gene and sequenced in Illumina platform. Microbiota analyses included sample-to-sample distance metrics, ordination/clustering and prediction of functions. Presence of Nesterenkonia sp. and Helicobacter pylori cagA and vacA genes were tested in the 100 ECCA and 100 BBP samples. Phylum Proteobacteria dominated all samples (60.4% average). Ordination multicomponent analyses showed significant microbiota separation between ECCA and BBP (p 0.010). Analyses of 4002 operational taxonomic units with presence variation in at least one category probed a separation of ECCA from BBP. Among these, Nesterenkonia decreased, whereas Methylophilaceae, Fusobacterium, Prevotella, Actinomyces, Novosphingobium and H. pylori increased in ECCA. Predicted associated functions showed increased abundance of H. pylori virulence genes in ECCA. cagA and vacA genes were confirmed by PCR in ECCA and BBP samples. This is the first microbiota report in ECCA and BBP to show significant changes in microbial composition. Bacterial species unusual for human flora were found: Methylophilaceae and Nesterenkonia are reported in hypersaline soils, and Mesorhizobium is a nitrogen-fixing bacterium. Enrichment of virulence genes confirms previous studies suggesting that H. pylori might be associated with ECCA. PMID:26493848

Biliary anatomy and its common and uncommon variations are of considerable clinical significance when performing living donor transplantation, radiological interventions in hepatobiliary system, laparoscopic cholecystectomy, and liver resection (hepatectomy, segmentectomy). Because of increasing trend found in the number of liver transplant surgeries being performed, magnetic resonance cholangiopancreatography (MRCP) has become the modality of choice for noninvasive evaluation of abnormalities of the biliary tract. The purpose of this study is to describe the anatomic variations of the intrahepatic and extrahepatic biliary tree. PMID:27081220

Background. In order to assess the diagnostic accuracy of linear EUS for evaluating clinically suggestive CBD stones in high-risk groups. Methods. 202 patients with clinically suggestive CBD stones in high-risk groups who underwent linear EUS examination between January 2012 and January 2015 were retrospectively reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction or surgical choledochoscopy was only performed when a CBD stone was detected by linear EUS. Cases that were negative for CBD stones were followed up for at least 6 months. Results. Of 202 enrolled patients, 126 were positive for CBD stones according to linear EUS findings. 124 patients successfully underwent ERCP, and ERCP failed in 2 who were later successfully treated by surgical intervention. There were 2 false-positive cases with positive findings for CBD stones on ERCP. Among 76 patients without CBD stones, no false-negative cases were identified during the mean 6-month follow-up. Linear EUS had sensitivity, specificity, and positive and negative predictive values for the detection of CBD stones of 100%, 92.88%, 98.21%, and 100%, respectively. Conclusions. Linear EUS is a safe and efficacious diagnostic tool for evaluating clinically suggestive CBD stones with high risk of choledocholithiasis. Performing linear EUS prior to ERCP in patients with symptoms suggestive of CBD stones can reduce unnecessary ERCP procedures. PMID:27610131

The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers. PMID:27276097

A crude ethanol extract of Kaemperia parviflora Wall. Ex Baker and a purified compound, 5,7,4-trimethoxyflavone (KP.8.10), were evaluated for pharmacological effects on human cholangiocarcinoma cell lines (HuCCA-1 and RMCCA-1). The cells were incubated with various concentrations of extract for various time periods and metabolic activity (MTT assay) was assessed for cell viability. The results showed a dose-dependent effect of both crude ethanol extract and the pure compound. CC50s for the crude extract on HuCCA-1 and RMCCA-1 cells were 46.1 microg/ml and 62.0 microg/ml, respectively. Values for the pure compound could not be determined because of solubility problems. Interestingly, K. parviflora ethanol extract and KP.8.10 at low concentrations (10-20 microg/ml and 2.5-5 microg/ml, respectively) markedly reduced rhHGF-induced invasion by HuCCA-1 and RMCCA-1 cells across matrix-coated transwell plates. Higher concentrations of K. parviflora ethanol extract (60 and 80 microg/ml) and KP.8.10 (20 microg /ml) dramatically changed the cellular morphology and caused death in both cell types. KP.8.10 further exhibited progressive action via caspase-3 mitochondrial enzyme activation, enhancing cellular toxicity in a time-dose dependent fashion. Therefore, 5,7,4-trimethoxyflavone appeared to be a bioactive component of K. parviflora extract capable of exerting anti-cancer action. The results suggested a benefit of this edible plant in prevention and treatment of cholangiocarcinoma. PMID:19827897

Background. In order to assess the diagnostic accuracy of linear EUS for evaluating clinically suggestive CBD stones in high-risk groups. Methods. 202 patients with clinically suggestive CBD stones in high-risk groups who underwent linear EUS examination between January 2012 and January 2015 were retrospectively reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction or surgical choledochoscopy was only performed when a CBD stone was detected by linear EUS. Cases that were negative for CBD stones were followed up for at least 6 months. Results. Of 202 enrolled patients, 126 were positive for CBD stones according to linear EUS findings. 124 patients successfully underwent ERCP, and ERCP failed in 2 who were later successfully treated by surgical intervention. There were 2 false-positive cases with positive findings for CBD stones on ERCP. Among 76 patients without CBD stones, no false-negative cases were identified during the mean 6-month follow-up. Linear EUS had sensitivity, specificity, and positive and negative predictive values for the detection of CBD stones of 100%, 92.88%, 98.21%, and 100%, respectively. Conclusions. Linear EUS is a safe and efficacious diagnostic tool for evaluating clinically suggestive CBD stones with high risk of choledocholithiasis. Performing linear EUS prior to ERCP in patients with symptoms suggestive of CBD stones can reduce unnecessary ERCP procedures. PMID:27610131

For many years, bile acids were thought to only function as detergents which solubilize fats and facilitate the uptake of fat-soluble vitamins in the intestine. Many early observations; however, demonstrated that bile acids regulate more complex processes, such as bile acids synthesis and immune cell function through activation of signal transduction pathways. These studies were the first to suggest that receptors may exist for bile acids. Ultimately, seminal studies by many investigators led to the discovery of several bile acid-activated receptors including the farnesoid X receptor, the vitamin D receptor, the pregnane X receptor, TGR5, α5 β1 integrin, and sphingosine-1-phosphate receptor 2. Several of these receptors are expressed outside of the gastrointestinal system, indicating that bile acids may have diverse functions throughout the body. Characterization of the functions of these receptors over the last two decades has identified many important roles for these receptors in regulation of bile acid synthesis, transport, and detoxification; regulation of glucose utilization; regulation of fatty acid synthesis and oxidation; regulation of immune cell function; regulation of energy expenditure; and regulation of neural processes such as gastric motility. Through these many functions, bile acids regulate many aspects of digestion ranging from uptake of essential vitamins to proper utilization of nutrients. Accordingly, within a short time period, bile acids moved beyond simple detergents and into the realm of complex signaling molecules. Because of the important processes that bile acids regulate through activation of receptors, drugs that target these receptors are under development for the treatment of several diseases, including cholestatic liver disease and metabolic syndrome. In this review, we will describe the various bile acid receptors, the signal transduction pathways activated by these receptors, and briefly discuss the physiological processes that

We have previously shown that chenodeoxycholic acid (CDCA) strongly inhibits pancreatic ductal HCO3 (-) secretion through the destruction of mitochondrial function, which may have significance in the pathomechanism of acute pancreatitis (AP). Ursodeoxycholic acid (UDCA) is known to protect the mitochondria against hydrophobic bile acids and has an ameliorating effect on cell death. Therefore, our aim was to investigate the effect of UDCA pretreatment on CDCA-induced pancreatic ductal injury. Guinea pig intrainterlobular pancreatic ducts were isolated by collagenase digestion. Ducts were treated with UDCA for 5 and 24 h, and the effect of CDCA on intracellular Ca(2+) concentration ([Ca(2+)]i), intracellular pH (pHi), morphological and functional changes of mitochondria, and the rate of apoptosis were investigated. AP was induced in rat by retrograde intraductal injection of CDCA (0.5%), and the disease severity of pancreatitis was assessed by measuring standard laboratory and histological parameters. Twenty-four-hour pretreatment of pancreatic ducts with 0.5 mM UDCA significantly reduced the rate of ATP depletion, mitochondrial injury, and cell death induced by 1 mM CDCA and completely prevented the inhibitory effect of CDCA on acid-base transporters. UDCA pretreatment had no effect on CDCA-induced Ca(2+) signaling. Oral administration of UDCA (250 mg/kg) markedly reduced the severity of CDCA-induced AP. Our results clearly demonstrate that UDCA 1) suppresses the CDCA-induced pancreatic ductal injury by reducing apoptosis and mitochondrial damage and 2) reduces the severity of CDCA-induced AP. The protective effect of UDCA against hydrophobic bile acids may represent a novel therapeutic target in the treatment of biliary AP. PMID:26608189

It is pointed out that the great temperature difference between the outside of a cryogenic duct and the liquified gas it carries can cause a high heat input unless blocked by a high thermal resistance. High thermal resistance for lines needing maximum insulation is provided by metal vacuum jackets. Low-density foam is satisfactory in cases in which higher heat input can be tolerated. Attention is given to the heat transfer through a duct vacuum jacket, the calculation of heat input and the exterior surface's steady-state temperature for various thicknesses of insulation, the calculation of the heat transfer through gimbal jackets, and design specifications regarding the allowable pressure rise in the jacket's annular space.

We examine the radial spoke pattern evident in the meniscus region in glasses of strong alcoholic beverages exhibiting the `tears-in-wine' phenomenon. We demonstrate that the pattern results from ridge-like elevations of the free surface which are supported by evaporatively-driven Marangoni convection in the meniscus region. Vortices associated with the convective motions are aligned in the radial direction by the surface tension gradient responsible for the generation of tears. The radial flow is focussed into the ridges, which thus serve as the principal conduits of fluid for the tears; consequently, we refer to the ridges as `tear-ducts'. The phenomenon is examined experimentally, and a numerical model of evaporatively-driven Marangoni convection is developed which reproduces the salient features of the tear-duct phenomenon.

It is well known that strong electron heating by a powerful HF-facility can lead to the formation of electron and ion density perturbations that stretch along the magnetic field line. Those density perturbations can serve as ducts for ELF waves, both of natural and artificial origin. This paper presents observations of the plasma density perturbations caused by the HF-heating of the ionosphere by the HAARP facility. The low orbit satellite DEMETER was used as a diagnostic tool to measure the electron and ion temperature and density along the satellite orbit overflying close to the magnetic zenith of the HF-heater. Those observations will be then checked against the theoretical model of duct formation due to HF-heating of the ionosphere. The model is based on the modified SAMI2 code, and is validated by comparison with well documented experiments.

Research over the last decade has uncovered roles for bile acids (BAs) that extend beyond their traditional functions in regulating lipid digestion and cholesterol metabolism. BAs are now recognized as signaling molecules that interact with both plasma membrane and nuclear receptors. Emerging evidence indicates that by interacting with these receptors BAs regulate their own synthesis, glucose and energy homeostasis, and other important physiological events. Herein, we provide a comprehensive review of the actions of BAs on cardiovascular function. In the heart and the systemic circulation, BAs interact with plasma membrane G-protein coupled receptors, e.g. TGR5 and muscarinic receptors, and nuclear receptors, e.g. the farnesoid (FXR) and pregnane (PXR) xenobiotic receptors. BA receptors are expressed in cardiovascular tissue, however, the mechanisms underlying BA-mediated regulation of cardiovascular function remain poorly understood. BAs reduce heart rate by regulating channel conductance and calcium dynamics in sino-atrial and ventricular cardiomyocytes, and regulate vascular tone via both endothelium-dependent and -independent mechanisms. End-stage-liver disease, obstructive jaundice and intrahepatic cholestasis of pregnancy are prominent conditions in which elevated serum BAs alter vascular dynamics. This review focuses on BAs as newly-recognized signaling molecules that modulate cardiovascular function. PMID:21707953

A 52-year-old woman presented with relapsing acute pancreatitis. A contrast CT scan revealed polysplenia, agenesis of the dorsal pancreas, preduodenal portal vein, inferior vena cava with persistent continuity of the azygos vein, abnormal lung lobation with bilateral left bronchial morphology, and intestinal malrotation (non-rotation type). To the best of our knowledge, this is the first report in which successful pancreatic duct stent placement for the treatment of recurrent pancreatitis was performed in a polysplenia patient with agenesis of the dorsal pancreas, separate bile and pancreatic ducts and Peutz-Jeghers syndrome. PMID:27374675

The bile salt independent fraction (BSIF) of canalicular bile flow from the isolated rat liver perfused with bicarbonate-free perfusate is 50% of that from the liver perfused with bicarbonate-containing perfusate. HCO3-excretion is nearly eliminated and Na+ and Cl- excretion is reduced 50%. Replacement of HCO3- into perfusate increased bile flow by 0.3 microliter/g.min without changing bile acid excretion rate. 5.5-Dimethyl-2,4-oxazolidinedione (DMO) produced a similar effect. DMO was passively distributed between bile and plasma. The data indicate that a bicarbonate transport mechanism is responsible for production of up to 50% of the BSIF. Another weak acid, N-5[5-(2-methoxyethoxy)-2-pyrimidinyl]sulfamoylbenzene (glymidine), was rapidly excreted into bile and increased bile flow by over 2.0 microliter/g.min. Glymidine is probably excreted by an independent organic anion transport mechanism, and any effect on the bicarbonate transport mechanism is obscured. Canaliculus-enriched hepatocyte membrane fractions contained no HCO3-stimulated ATPase activity. Either this enzyme is unimportant in hepatocyte bicarbonate transport or transport occurs across membranes other than the bile canalicular membrane. PMID:150796

1. The transcription factor Nrf2 is important for hepatoprotection against oxidative stress, as it regulates many cytoprotective genes, including several important for glutathione (GSH) homeostasis. In addition to being an important endogenous antioxidant, GSH is also critical for the maintenance of bile acid-independent bile flow. While it has been well-established that synthetic oleanane triterpenoids pharmacologically activate Nrf2, their effects on bile flow and hepatic cytoprotective capacity have not been fully explored. 2. The present studies were conducted to evaluate the effects of a compound in this class, CDDO-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA), on these parameters. CDDO-dhTFEA at 3, 10 or 30 mg/kg was orally administered to bileduct-cannulated rats once daily for 7 days, with bile collected 5 h after each dose for 1 h. Livers were harvested after the final bile collection for the evaluation of histology and Nrf2 targets. 3. CDDO-dhTFEA did not affect liver histology. CDDO-dhTFEA markedly and dose-dependently increased bile flow, as well as the biliary excretion of GSH, cholesterol and phospholipids without affecting biliary excretion of bile acids. This was accompanied by dose-dependent increases in mRNA expression and/or enzyme activity of a broad panel of cytoprotective Nrf2 target genes, including NAD(P)H quinone oxidoreductase 1 (Nqo1), thioredoxin reductase (Txnrd), sulfiredoxin 1(Srxn1), glutamate cysteine ligase catalytic and modifier subunits (Gclc and Gclm), glutathione reductase (Gsr), gamma-glutamyl transpeptidase 1 (Ggt1), heme oxygenase-1 (Ho-1) and epoxide hydrolase-1 (Eh-1). 4. These data further demonstrate the important hepatobiliary attributes of oleanane synthetic triterpenoids and support their continued investigation for liver diseases. PMID:23244591

Empirical equations were developed and applied to predict losses of 0.01-100 {micro}m airborne particles making a single pass through 120 different ventilation duct runs typical of those found in mid-sized office buildings. For all duct runs, losses were negligible for submicron particles and nearly complete for particles larger than 50 {micro}m. The 50th percentile cut-point diameters were 15 {micro}m in supply runs and 25 {micro}m in return runs. Losses in supply duct runs were higher than in return duct runs, mostly because internal insulation was present in portions of supply duct runs, but absent from return duct runs. Single-pass equations for particle loss in duct runs were combined with models for predicting ventilation system filtration efficiency and particle deposition to indoor surfaces to evaluate the fates of particles of indoor and outdoor origin in an archetypal mechanically ventilated building. Results suggest that duct losses are a minor influence for determining indoor concentrations for most particle sizes. Losses in ducts were of a comparable magnitude to indoor surface losses for most particle sizes. For outdoor air drawn into an unfiltered ventilation system, most particles smaller than 1 {micro}m are exhausted from the building. Large particles deposit within the building, mostly in supply ducts or on indoor surfaces. When filters are present, most particles are either filtered or exhausted. The fates of particles generated indoors follow similar trends as outdoor particles drawn into the building.

Characterization of ox bile, traditionally used in painting, is of interest in the fields of archaeometry and conservation and restoration of works of art. Bile acids, fatty acids (F), and cholesterol found in ox bile have been identified using a derivatization method that combines the formation of ethyl esters from the carboxylic groups and the trimethylsilyl ethers from hydroxyl groups. This method of analysis is consistent with these others proposed by the authors to analyze drying oils, proteins, and diterpenic resins usually used as binders and varnishes by the painters. Bile acids from binary samples such as animal glue/ox bile, casein/ox bile and Arabic gum/ox bile have been successfully analyzed using the proposed method. Finally, a method of analysis of mixtures of drying oil and ox bile has been also proposed attempting to quantitatively characterize samples in which ox bile was added to the drying oil for increasing the surfactant properties. PMID:14763811

The concentrative nucleoside transporter-1 (CNT1) is a member of the solute carrier 28 (SLC28) gene family and is expressed in the liver, intestine, and kidneys. CNT1 mediates the uptake of naturally occurring pyrimidine nucleosides, but also nucleoside analogs used in anticancer and antiviral therapy. Thus expression levels of CNT1 may affect the pharmacokinetics of these drugs and the outcome of drug therapy. Because little is known about the transcriptional regulation of human CNT1 gene expression, we have characterized the CNT1 promoter with respect to DNA response elements and their binding factors. The transcriptional start site of the CNT1 gene was determined by 5'-RACE. In silico analysis revealed the existence of three putative binding sites for the nuclear receptor hepatocyte nuclear factor-4alpha (HNF-4alpha) within the CNT1 promoter. A luciferase reporter gene construct containing the CNT1 promoter region was transactivated by HNF-4alpha in human cell lines derived from the liver, intestine, and kidneys. Consistent with this, we showed in electromobility shift assays that HNF-4alpha specifically binds to two conserved direct repeat-1 motifs within the proximal CNT1 promoter. In cotransfection experiments, the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha further increased, whereas the bile acid-inducible corepressor small heterodimer partner reduced, HNF-4alpha-dependent CNT1 promoter activity. Consistent with the latter phenomenon, CNT1 mRNA expression levels were suppressed in primary human hepatocytes upon bile acid treatment. Supporting the physiological relevance and species conservation of this effect, ileal Cnt1 mRNA expression was decreased upon bile acid feeding and increased upon bileduct ligation in mice. PMID:19228884

Mg-6Zn alloy was studied as candidate biodegradable metallic implants for the common bileduct (CBD) in terms of its in vitro corrosion and in vivo corrosion. Electrochemical measurements, immersion tests and hydrogen evolution were performed in the bile and Hanks' solution to evaluate the in vitro degradation behavior of Mg-6Zn alloy. The results showed that the degradation rate and hydrogen evolution were higher when Mg-6Zn alloy immersed in the bile than in the Hanks' solution. The polarization resistance of the samples in the Hanks' solution was about 1.5 times to that in the bile. In the in vivo experiment, Mg-6Zn alloy stents were inserted in CBD of 42 rabbits, and CT scans, the value of total bilirubin (TB) and in vivo corrosion rate were determined. From the results of CT images and the fluctuations of TB values, it can be seen that the stent was degraded gradually in CBD. After 1 week post-implantation, the majority of the Mg-6Zn alloy sample remained in the CBD. Usually the required support time for CBD stent was approximately 7-10 days, thus the Mg-6Zn alloy stent was very close to the clinical requirement for CBD support materials. After three weeks, the residual weight of the Mg-6Zn alloy was only 9% of the original weight. The in vivo corrosion rate of Mg-6Zn alloy was ~0.107 mm·year(-1), which was much lower than that calculated in vitro (~0.72 mm·year(-1) by electrochemical test). Based on our research, there is promising for the Mg-6Zn alloy in CBD applications. PMID:25063100

Twenty-eight patients with radiolucent biliary duct stones without cholangitis and jaundice were randomly allocated into two treatment groups receiving ursodeoxycholic acid 12 mg/kg (group A) or placebo (group B) in three daily doses for 24 months. In group A stones disappeared completely in seven patients and partially in one; placebo administration had no effect on stone size and three patients of group B (only one of group A) went to surgery for complications. Ursodeoxycholic acid treatment did not adversely affect liver function tests, and alkaline phosphatase decreased. Abdominal and biliary colics also became less frequent in the first six months of therapy in group A, but not in the placebo group. The bile was supersaturated with cholesterol in both groups, but decreased significantly only in patients receiving ursodeoxycholic acid even though the lithogenic index remained high. Cholesterol saturation of bile does not seem to be the only factor determining the dissolution of biliary duct stones which sometimes contain cholesterol as the main component. PMID:6345281

Bile salts play crucial roles in allowing the gastrointestinal system to digest, transport and metabolize nutrients. They function as nutrient signaling hormones by activating specific nuclear receptors (FXR, PXR, Vitamin D) and G-protein coupled receptors [TGR5, sphingosine-1 phosphate receptor 2 (S1PR2), muscarinic receptors]. Bile acids and insulin appear to collaborate in regulating the metabolism of nutrients in the liver. They both activate the AKT and ERK1/2 signaling pathways. Bile acid induction of the FXR-α target gene, small heterodimer partner (SHP), is highly dependent on the activation PKCζ, a branch of the insulin signaling pathway. SHP is an important regulator of glucose and lipid metabolism in the liver. One might hypothesize that chronic low grade inflammation which is associated with insulin resistance, may inhibit bile acid signaling and disrupt lipid metabolism. The disruption of these signaling pathways may increase the risk of fatty liver and non-alcoholic fatty liver disease (NAFLD). Finally, conjugated bile acids appear to promote cholangiocarcinoma growth via the activation of S1PR2. PMID:24819989

Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles in bile acid synthesis. Bile acids are physiological detergent molecules, so are highly cytotoxic. They undergo enterohepatic circulation and play important roles in generating bile flow and facilitating biliary secretion of endogenous metabolites and xenobiotics and intestinal absorption of dietary fats and lipid soluble vitamins. Bile acid synthesis, transport and pool size are therefore tightly regulated under physiological conditions. In cholestasis, impaired bile flow leads to accumulation of bile acids in the liver, causing hepatocyte and biliary injury and inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis and eventually liver failure. Chronic cholestasis also increases the risk of developing hepatocellular or cholangiocellular carcinomas. Extensive research in the last two decades has shown that bile acids act as signaling molecules that regulate various cellular processes. The bile acid-activated nuclear receptors are ligand-activated transcriptional factors that play critical roles in the regulation of bile acid, drug and xenobiotic metabolism. In cholestasis, these bile acid-activated receptors regulate a network of genes involved in bile acid synthesis, conjugation, transport and metabolism to alleviate bile acid-induced inflammation and injury. Additionally, bile acids are known to regulate cell growth and proliferation, and altered bile acid levels in diseased conditions have been implicated in liver injury/regeneration and tumorigenesis. We will cover the mechanisms that regulate bile acid homeostasis and detoxification during cholestasis, and the roles of bile acids in the initiation and regulation of hepatic inflammation, regeneration and carcinogenesis. PMID:26233910

A combined turbofan and ramjet aircraft engine includes a forward bypass duct which allows the engine to operate more efficiently during the turbofan mode of operation. By mounting a ramjet preburner in the forward duct and isolating this duct from the turbofan bypass air, a transition from turbofan operation to ramjet operation can take place at lower flight Mach numbers without incurring pressure losses or blockage in the turbofan bypass air.

Parotid salivary duct dilation was diagnosed in a 9-year-old male dog. The dog had undergone caudal maxillectomy on the ipsilateral side 2-years prior to presentation. Treatment consisted of parotid salivary duct excision and superficial parotidectomy that lead to the resolution of clinical signs. Transient facial neuropraxia was observed immediately after surgery and resolved spontaneously after 2-weeks. Parotid salivary duct dilation should be considered as a chronic postoperative complication following caudal maxillectomy. PMID:24902412

Injuries to the thoracic duct are infrequent but may become life-threatening when chylous leakage persists. This report describes 6 patients with such injuries in whom the leakage resolved spontaneously in one, was corrected using microsurgical lymphatic repair or lymphatic-venous anastomosis in two, successfully treated either by ligation of the thoracic duct or insertion of a peritoneovenous shunt in two, and was eventually controlled after bilateral pleurodesis and thoracic duct ligation by insertion of a peritoneo-venous shunt in one. Conventional lymphography is superior to lymphoscintigraphy and is usually required to document disruption of the thoracic duct. PMID:11939572

Generator stator cores are constructed by stacking many layers of magnetic laminations. Ventilation ducts may be inserted between these layers by inserting spacers into the core stack. The ventilation ducts allow for the passage of cooling gas through the core during operation. The spacers or spacer posts are positioned between groups of the magnetic laminations to define the ventilation ducts. The spacer posts are secured with longitudinal axes thereof substantially parallel to the core axis. With this structure, core tightness can be assured while maximizing ventilation duct cross section for gas flow and minimizing magnetic loss in the spacers.

Purpose. Laparoscopic cholecystectomy (LC) is the treatment of choice for gallstones. There is an increased incidence of bileduct injuries in LC compared with the open technique. Isolated right segmental hepatic duct injury (IRSHDI) represents a challenge not only for management but also for diagnosis. We present our experience in the management of IRSHDI, with long-term follow-up after treatment by a multidisciplinary approach. Methods. Twelve consecutive patients (9 women, mean age 48 years) were identified as having IRSHDI. Patients' demographics, clinical presentation, management and outcome were collected for analysis. The mean follow-up was 44 months (range 2-90 months). Results. Three patients had the LC immediately converted to open surgery without repair of the biliary injury before referral. Treatments before referral included endoscopic retrograde cholangiopancreatography (ERCP), percutaneous drainage and surgery, isolated or in combination. The median interval from LC to referral was 32 days. Eleven patients presented with biliary leak and biloma, one with obstruction of an isolated right hepatic segment. Post-referral management of the biliary lesion used a combination of ERCP stenting, percutaneous drainage and stent placement and surgery. In 6 of 12 patients ERCP was the first procedure, and in only one case was IRSHDI identified. In 6 patients, percutaneous transhepatic cholangiography (PTC) was performed first and an isolated right hepatic segment was demonstrated in all. The final treatment modality was endoscopic management and/or percutaneous drainage and stenting in 6 patients, and surgery in 6. The mean follow-up was 44 months. No mortality or significant morbidity was observed. Conclusion. Successful management of IRSHDI after LC requires adequate identification of the lesion, and multidisciplinary treatment is necessary. Half of the patients can be treated successfully by nonsurgical procedures.

The first generation of easily-retrofitable duct-injection technologies experienced problems with modest performance, particulate non-compliance, and difficult waste disposal. A new sorbent concept, called Fluesorbent, has been developed specifically to address these problems. Based on a new lime sorbent material, the technology results in 80+% SO{sub 2} removal, net particulate reductions, and a valuable agricultural by-product instead of wastes. A 6,500 acfm, 2-MWe Fluesorbent pilot plant was recently constructed at Ohio Edison`s R.E. Burger station. This paper describes the technology and the Burger demonstration project.

Bile acids constitute a group of structurally closely related molecules and represent the most abundant constituents of human bile. Investigations of bile acids have garnered increased interest owing to their recently discovered additional biological functions including their role as signaling molecules that govern glucose, fat and energy metabolism. Recent NMR methodological developments have enabled single-step analysis of several highly abundant and common glycine- and taurine- conjugated bile acids, such as glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid. Investigation of these conjugated bile acids in human bile employing high field (800 MHz) (1)H-NMR spectroscopy reveals that the ratios between two glycine-conjugated bile acids and their taurine counterparts correlate positively (R2 = 0.83-0.97; p = 0.001 x 10(-2)-0.006 x 10(-7)) as do the ratios between a glycine-conjugated bile acid and its taurine counterpart (R2 = 0.92-0.95; p = 0.004 x 10(-3)-0.002 x 10(-10)). Using such correlations, concentration of individual bile acids in each sample could be predicted in good agreement with the experimentally determined values. These insights into the pattern of bile acid conjugation in human bile between glycine and taurine promise useful clues to the mechanism of bile acids' biosynthesis, conjugation and enterohepatic circulation, and may improve our understanding of the role of individual conjugated bile acids in health and disease. PMID:19373503

The classical representation of the semicircular duct system consists of three separate duct circuits. The ducts are, however, in reality, hydrodynamically interconnected. Muller & Verhagen (1988a,b) derived equations for the mechanical behaviour of an interconnected system with three ducts (anterior, posterior and horizontal). An analytical solution of these equations would, however, be too complex to provide surveyable formulae. A system of two interconnected ducts avoids this complexity whilst keeping the essentials of the coupling of ducts intact. The solution of the equation of motion leads to expressions for time constants and maximal endolymph excursions which are functions of morphological parameters, viz. the ratios of radi